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In
biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms, Developmenta ...
, cell signaling (cell signalling in
British English British English (BrE) is the standard dialect of the English language English is a West Germanic languages, West Germanic language first spoken in History of Anglo-Saxon England, early medieval England, which has eventually become the ...
) or cell communication is the ability of a
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Closed spaces * Monastic cell, a small room, hut, or cave in which a monk or religious recluse lives * Prison cell, a room used to hold peopl ...
to receive, process, and transmit signals with its environment and with itself. It is a fundamental property of all cells in every living organism such as bacteria, plants, and animals. Signals that originate from outside a cell (or extracellular signals) can be physical agents like mechanical
pressure Pressure (symbol: ''p'' or ''P'') is the force In physics Physics (from grc, φυσική (ἐπιστήμη), physikḗ (epistḗmē), knowledge of nature, from ''phýsis'' 'nature'), , is the natural science that studies ma ...

pressure
, voltage,
temperature Temperature is a physical quantity that expresses hot and cold. It is the manifestation of thermal energy, present in all matter, which is the source of the occurrence of heat, a flow of energy, when a body is in contact with another that is ...

temperature
, light, or chemical signals (e.g., small molecules,
peptide Peptides (from Greek language πεπτός, ''peptós'' "digested"; derived from πέσσειν, ''péssein'' "to digest") are short chains of amino acids linked by peptide bonds. Chains of fewer than ten or fifteen amino acids are called oligopep ...
s, or gas). Chemical signals can be hydrophobic or hydrophillic. Cell signaling can occur over short or long distances, and as a result can be classified as
autocrineAutocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with p ...
,
juxtacrine In biology, juxtacrine signalling (or contact-dependent signalling) is a type of cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Closed spaces * Monastic cell, a small room, hut, or ca ...
,
intracrine Intracrine refers to a hormone A hormone (from the Greek participle , "setting in motion") is any member of a class of signaling molecules in multicellular organisms, that are transported to distant organs to regulate physiology and / or behavi ...
,
paracrineParacrine signaling is form of cell signaling or cell-to-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a rel ...
, or
endocrine The endocrine system is a messenger system comprising feedback loops of the hormone A hormone (from the Greek participle , "setting in motion") is any member of a class of signaling molecules in multicellular organisms, that are transported ...
. Signaling molecules can be synthesized from various biosynthetic pathways and released through passive or
active transport In cellular biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processe ...
s, or even from
cell damage Cell damage (also known as cell injury) is a variety of changes of stress that a cell suffers due to external as well as internal environmental changes. Amongst other causes, this can be due to physical, chemical, infectious, biological, nutritional ...
. Receptors play a key role in cell signaling as they are able to detect chemical signals or physical stimuli. Receptors are generally proteins located on the cell surface or within the interior of the cell such as the
cytoplasm In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, ...
,
organelle In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, M ...
s, and nucleus.
Cell surface receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane cell membrane vs. Prokaryotes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and ...
s usually bind with extracellular signals (or ligands), which causes a
conformational change 300px, Conformational changes can elicit the motion of a protein complex. Kinesin walking on a microtubule">Kinesin.html" ;"title="protein complex. Kinesin">protein complex. Kinesin walking on a microtubule is a molecular biological machine using ...

conformational change
in the receptor that leads it to initiate enzymic activity, or to open or close
ion channel s (typically four per channel), 2 - outer vestibule, 3 - Potassium channel#Selectivity filter, selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane. Ion channels are pore-forming membrane proteins that ...

ion channel
activity. Some receptors do not contain enzymatic or channel-like domains but are instead linked to enzymes or transporters. Other receptors like
nuclear receptor of a heterodimer of the nuclear receptors PPAR-γ (green) and RXR-α (cyan) bound to double stranded DNA The structure of part of a DNA double helix Deoxyribonucleic acid (; DNA) is a molecule File:Pentacene on Ni(111) STM.jpg, A sca ...
s have a different mechanism such as changing their
DNA The structure of part of a DNA double helix Deoxyribonucleic acid (; DNA) is a molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings ...
binding properties and cellular localization to the nucleus.
Signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation residue Protein phosphorylation is a reversible post-translational m ...
begins with the transformation (or transduction) of a signal into a chemical one, which can directly activate an ion channel (
ligand-gated ion channel Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane Image:Polytopic membrane protein.png, 400px, Schematic representation of transmembrane proteins: 1) a single transmembrane ...
) or initiate a
second messenger system Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intracellular signals, a non-local form or cell signaling In biology Biology is ...
cascade that propagates the signal through the cell. Second messenger systems can amplify a signal, in which activation of a few receptors results in multiple secondary messengers being activated, thereby amplifying the initial signal (the first messenger). The downstream effects of these signaling pathways may include additional enzymatic activities such as
proteolytic cleavage A protease (also called a peptidase or proteinase) is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (c ...

proteolytic cleavage
,
phosphorylation In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds composed of atoms, molecules and ions: their composition, structure, properties, behavior and the changes they unde ...

phosphorylation
,
methylation In the chemical sciences, methylation denotes the addition of a methyl, methyl group on a Substrate (chemistry), substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replaci ...

methylation
, and
ubiquitinylation Ubiquitin is a small (8.6 atomic mass unit, kDa) regulatory protein found in most tissues of eukaryotes, eukaryotic organisms, i.e., it is found :wiktionary:ubiquitous, ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further ch ...
. Each cell is programmed to respond to specific extracellular signal molecules, and is the basis of
development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking#Development, Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material i ...
,
tissue repair Tissue engineering is a biomedical engineering discipline that uses a combination of cells, engineering Engineering is the use of scientific method, scientific principles to design and build machines, structures, and other items, includ ...
, immunity, and
homeostasis In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms ...
. Errors in signaling interactions may cause diseases such as
cancer Cancer is a group of diseases A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not due to any immediate external injury. Diseases are often kn ...

cancer
,
autoimmunity Autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other body normal constituents. Any disease that results from such an aberrant immune response is termed an " autoimmune disease". Prominent e ...
, and
diabetes Diabetes mellitus (DM), commonly known as diabetes, is a group of metabolic disorders characterized by a high blood sugar level over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased appeti ...
.


Taxonomic range

In many small organisms such as
bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a Bacte ...
,
quorum sensingIn biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms, De ...
enables individuals to begin an activity only when the population is sufficiently large. This signaling between cells was first observed in the marine bacterium ''
Aliivibrio fischeri ''Aliivibrio fischeri'' (also called ''Vibrio fischeri'') is a Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram stain, gram-staining method of bacterial differentiation. They are char ...

Aliivibrio fischeri
'', which produces light when the population is dense enough. The mechanism involves the production and detection of a signaling molecule, and the regulation of gene transcription in response. Quorum sensing operates in both gram-positive and gram-negative bacteria, and both within and between species. In
slime mould Slime mold or slime mould is an informal name given to several kinds of unrelated eukaryotic Eukaryotes () are organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual ...
s, individual cells known as amoebae aggregate together to form fruiting bodies and eventually spores, under the influence of a chemical signal, originally named
acrasinEach species of slime mold has its own specific chemical messenger, which are collectively referred to as acrasins. These chemicals signal that many individual cells aggregate to form a single large cell or Plasmodium (life cycle), plasmodium. One of ...
. The individuals move by
chemotaxis Chemotaxis (from '' chemo-'' + '' taxis'') is the movement of an organism in response to a chemical stimulus. Somatic cells, bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They ...
, i.e. they are attracted by the chemical gradient. Some species use
cyclic AMP Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate Adenosine triphosphate (ATP) is an organic ...
as the signal; others such as '' Polysphondylium violaceum'' use other molecules, in its case N-propionyl-gamma-L-glutamyl-L-ornithine-delta-lactam ethyl ester, nicknamed glorin. In plants and animals, signaling between cells occurs either through release into the
extracellular space Extracellular space refers to the part of a multicellular organism outside the cell (biology), cells, usually taken to be outside the plasma membranes, and occupied by fluid. The composition of the extracellular space includes metabolites, ions, pr ...
, divided in
paracrineParacrine signaling is form of cell signaling or cell-to-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a rel ...
signaling (over short distances) and
endocrine The endocrine system is a messenger system comprising feedback loops of the hormone A hormone (from the Greek participle , "setting in motion") is any member of a class of signaling molecules in multicellular organisms, that are transported ...
signaling (over long distances), or by direct contact, known as juxtacrine signaling (e.g., notch signaling).
AutocrineAutocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with p ...
signaling is a special case of paracrine signaling where the secreting cell has the ability to respond to the secreted signaling molecule.
Synaptic
Synaptic
signaling is a special case of paracrine signaling (for
chemical synapse Chemical synapses are biological junctions through which neuron A neuron or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapse SyNAPSE is a DARPA program that aims t ...
s) or juxtacrine signaling (for
electrical synapse An electrical synapse is a mechanical and electrically conductive In physics and electrical engineering, a conductor is an object or type of material A material is a substance Substance may refer to: * Substance (Jainism), a term in Jain on ...
s) between
neuron A neuron or nerve cell is an membrane potential#Cell excitability, electrically excitable cell (biology), cell that communicates with other cells via specialized connections called synapses. It is the main component of nervous tissue in all Anima ...

neuron
s and target cells.


Extracellular signal


Synthesis and release

Many cell signals are carried by molecules that are released by one cell and move to make contact with another cell. Signaling molecules can belong to several chemical classes:
lipid In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms ...
s,
phospholipid Phospholipids, also known as phosphatides, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group, and two hydrophobic "tails" derived from fatty acids, joined by a glycerol molecule. The phosphate group ca ...

phospholipid
s,
amino acid Amino acids are organic compound , CH4; is among the simplest organic compounds. In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen chemical bond, bonds. Due to carbon's ability to Catenation, c ...
s,
monoamine Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromaticity, aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All mono ...
s,
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabol ...

protein
s,
glycoprotein Glycoproteins are protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme ...
s, or
gases Gas is one of the four fundamental states of matter (the others being solid Solid is one of the four fundamental states of matter (the others being liquid, gas and plasma). The molecules in a solid are closely packed together and c ...
. Signaling molecules binding surface receptors are generally large and
hydrophilic A hydrophile is a molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecule is an electrically neutral group of two or more atoms ...
(e.g. TRH,
Vasopressin Vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide Hormone, prohormone in neurons in the hypothalamus, and is converted to AVP. It then trav ...

Vasopressin
,
Acetylcholine Acetylcholine (ACh) is an organic chemical , CH4; is among the simplest organic compounds. In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds composed of atoms, mo ...

Acetylcholine
), while those entering the cell are generally small and
hydrophobic In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds composed of atoms, molecules and ions: their composition, structure, properties, behavior and the changes they ...
(e.g.
glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroid Corticosteroids are a class of steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: cor ...
s,
thyroid hormone File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones triiodothyronine, T3 and T4. rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rec ...
s,
cholecalciferol Cholecalciferol, also known as vitamin D3 and colecalciferol, is a type of vitamin D which is made by the skin when exposed to sunlight; it is also found in some foods and can be taken as a dietary supplement. Cholecalciferol is made in the ski ...

cholecalciferol
,
retinoic acid Retinoic acid (used simplified here for all-''trans''-retinoic acid) is a metabolite In biochemistry Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both c ...

retinoic acid
), but important exceptions to both are numerous, and a same molecule can act both via surface receptors or in an intracrine manner to different effects. In animal cells, specialized cells release these hormones and send them through the circulatory system to other parts of the body. They then reach target cells, which can recognize and respond to the hormones and produce a result. This is also known as endocrine signaling. Plant growth regulators, or plant hormones, move through cells or by diffusing through the air as a gas to reach their targets.
Hydrogen sulfide Hydrogen sulfide is a chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entity, molecular entities) composed of atoms from more than one chemical element, element held together by ...
is produced in small amounts by some cells of the human body and has a number of biological signaling functions. Only two other such gases are currently known to act as signaling molecules in the human body:
nitric oxide Nitric oxide ( nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical, i.e., it has an unpaired electron, which is sometimes denoted by a dot i ...
and
carbon monoxide Carbon monoxide (chemical formula CO) is a colorless, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom. It is the simplest molecule of the oxocarbon family. In ...
.


Exocytosis

Exocytosis Image:Synapse diag1.svg, 300px, Exocytosis of neurotransmitters into a synapse from neuron A to neuron B. Exocytosis () is a form of active transport and solvent drag, bulk transport in which a cell transports molecules (e.g., neurotransmitters an ...
is the process by which a cell transports
molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecule is an electrically neutral group of two or more atoms held together by chemical bo ...

molecule
s such as
neurotransmitter A neurotransmitter is a signaling molecule In biology, cell signaling (cell signalling in British English), or cell-cell communication, governs the basic activities of cells and coordinates multiple-cell actions. A signal is an entity that ...
s and
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabol ...

protein
s out of the cell. As an
active transport In cellular biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processe ...
mechanism, exocytosis requires the use of energy to transport material. Exocytosis and its counterpart,
endocytosis Endocytosis is a cellular process in which Chemical substance, substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a Vesicle (biology and chem ...

endocytosis
, are used by all cells because most
chemical substance A chemical substance is a form of matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are ultimately composed of atoms, which ...
s important to them are large
polar Polar may refer to: Geography Polar may refer to: * Geographical pole, either of two fixed points on the surface of a rotating body or planet, at 90 degrees from the equator, based on the axis around which a body rotates *Polar climate, the clim ...
molecules that cannot pass through the
hydrophobic In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds composed of atoms, molecules and ions: their composition, structure, properties, behavior and the changes they ...
portion of the
cell membrane cell membrane vs. Prokaryotes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates the interior of all cells from the out ...
by
passive Passive may refer to: * Passive voice, a grammatical voice common in many languages, see also Pseudopassive (disambiguation), Pseudopassive * Passive language, a language from which an interpreter works * Passivity (behavior), the condition of sub ...
means. Exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. Exocytosis occurs via secretory portals at the cell plasma membrane called
porosomes 280px Porosomes are cup-shaped supramolecular structures in the cell membranes of eukaryotic Eukaryotes () are organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual conti ...
.
Porosomes 280px Porosomes are cup-shaped supramolecular structures in the cell membranes of eukaryotic Eukaryotes () are organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual conti ...
are permanent cup-shaped lipoprotein structure at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell. In exocytosis, membrane-bound secretory
vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features of ...
are carried to the
cell membrane cell membrane vs. Prokaryotes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates the interior of all cells from the out ...
, where they dock and fuse at
porosomes 280px Porosomes are cup-shaped supramolecular structures in the cell membranes of eukaryotic Eukaryotes () are organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual conti ...
and their contents (i.e., water-soluble molecules) are secreted into the extracellular environment. This
secretionSecretion is the movement of material from one point to another, such as a secreted chemical substance A chemical substance is a form of matter In classical physics and general chemistry, matter is any substance that has mass and takes up sp ...
is possible because the vesicle transiently fuses with the plasma membrane. In the context of
neurotransmission 280px, The presynaptic neuron (top) releases a neurotransmitter, which activates receptors on the nearby postsynaptic cell (bottom). Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the pr ...
, neurotransmitters are typically released from
synaptic vesicle In a neuron, synaptic vesicles (or neurotransmitter vesicles) store various neurotransmitters that are exocytosis, released at the chemical synapse, synapse. The release is regulated by a voltage-dependent calcium channel. Vesicle (biology), Vesic ...
s into the
synaptic cleft Synaptic may refer to: * Synapse SyNAPSE is a DARPA program that aims to develop electronic neuromorphic machine technology, an attempt to build a new kind of cognitive computer with form, function, and architecture similar to the mammalian bra ...
via exocytosis; however, neurotransmitters can also be released via reverse transport through
membrane transport protein A membrane transport protein (or simply transporter) is a membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their loc ...
s.


Forms


Autocrine

Autocrine signaling involves a cell secreting a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell itself. This can be contrasted with
paracrine signalingParacrine signaling is form of cell signaling or cell-to-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a rel ...
,
intracrine Intracrine refers to a hormone A hormone (from the Greek participle , "setting in motion") is any member of a class of signaling molecules in multicellular organisms, that are transported to distant organs to regulate physiology and / or behavi ...
signaling, or classical
endocrine The endocrine system is a messenger system comprising feedback loops of the hormone A hormone (from the Greek participle , "setting in motion") is any member of a class of signaling molecules in multicellular organisms, that are transported ...
signaling.


Paracrine

In paracrine signaling, a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance (local action), as opposed to cell signaling by , hormones which travel considerably longer distances via the
circulatory system The circulatory system, also called the cardiovascular system or the vascular system, is an organ system that permits blood to circulate and transport nutrients (such as amino acids and electrolytes), oxygen, carbon dioxide, hormones, and blood ...
; juxtacrine interactions; and
autocrine signalingAutocrine signaling is a form of cell signaling In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular inter ...
. Cells that produce paracrine factors secrete them into the immediate
extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions f ...
environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain.
ParacrineParacrine signaling is form of cell signaling or cell-to-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a rel ...
signals such as
retinoic acid Retinoic acid (used simplified here for all-''trans''-retinoic acid) is a metabolite In biochemistry Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both c ...

retinoic acid
target only cells in the vicinity of the emitting cell.
Neurotransmitter A neurotransmitter is a signaling molecule In biology, cell signaling (cell signalling in British English), or cell-cell communication, governs the basic activities of cells and coordinates multiple-cell actions. A signal is an entity that ...
s represent another example of a paracrine signal. Some signaling molecules can function as both a hormone and a neurotransmitter. For example,
epinephrine Adrenaline, also known as epinephrine, is a hormone A hormone (from the Greek participle , "setting in motion") is any member of a class of signaling molecules in multicellular organisms, that are transported to distant organs to regulate p ...

epinephrine
and
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain A brain is an organ (anatomy), organ that serves as the center of the nervous system in all ...

norepinephrine
can function as hormones when released from the
adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal cortex ...
and are transported to the heart by way of the blood stream. Norepinephrine can also be produced by
neuron A neuron or nerve cell is an membrane potential#Cell excitability, electrically excitable cell (biology), cell that communicates with other cells via specialized connections called synapses. It is the main component of nervous tissue in all Anima ...

neuron
s to function as a neurotransmitter within the brain.
Estrogen Estrogens or oestrogens, are a class of natural or synthetic sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid hor ...

Estrogen
can be released by the
ovary The ovary is an organ found in the female reproductive system 400px, 1. Labia_majora.html"_;"title="Vulva: 2. Labia_majora">Vulva: 2. Labia_majora; 3. Labia_minora; 4. Vulval_vestibule.html" ;"title="Labia_minora.html" ...

ovary
and function as a hormone or act locally via paracrine or
autocrineAutocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with p ...
signaling. Although paracrine signaling elicits a diverse array of responses in the induced cells, most paracrine factors utilize a relatively streamlined set of receptors and pathways. In fact, different
organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tissues can be broadly cate ...
s in the body - even between different species - are known to utilize a similar sets of paracrine factors in differential development. The highly conserved receptors and pathways can be organized into four major families based on similar structures:
fibroblast growth factor Fibroblast growth factors (FGF) are a family of cell signalling protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array ...
(FGF) family,
Hedgehog A hedgehog is a spiny mammal of the subfamily Erinaceinae, in the eulipotyphlan family (biology), family Erinaceidae. There are seventeen species of hedgehog in five genus, genera found throughout parts of Europe, Asia, and Africa, and in New ...
family, Wnt family, and TGF-β superfamily. Binding of a paracrine factor to its respective receptor initiates
signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation residue Protein phosphorylation is a reversible post-translational m ...
cascades, eliciting different responses.


Endocrine

''
Endocrine The endocrine system is a messenger system comprising feedback loops of the hormone A hormone (from the Greek participle , "setting in motion") is any member of a class of signaling molecules in multicellular organisms, that are transported ...

Endocrine
'' signals are called
hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approximately 10.7 m ...

hormone
s. Hormones are produced by endocrine cells and they travel through the
blood Blood is a body fluid Body fluids, bodily fluids, or biofluids are liquid A liquid is a nearly incompressible fluid In physics, a fluid is a substance that continually Deformation (mechanics), deforms (flows) under an applied shear s ...
to reach all parts of the body. Specificity of signaling can be controlled if only some cells can respond to a particular hormone. Endocrine signaling involves the release of
hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approximately 10.7 m ...

hormone
s by internal
gland In animals, a gland is a group of cells in an animal's body that synthesizes substances (such as hormone A hormone (from the Greek participle , "setting in motion") is any member of a class of signaling molecules in multicellular organisms, ...

gland
s of an
organism In biology, an organism () is any organic, life, living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy (biology), taxonomy into groups such as Multice ...

organism
directly into the
circulatory system The circulatory system, also called the cardiovascular system or the vascular system, is an organ system that permits blood to circulate and transport nutrients (such as amino acids and electrolytes), oxygen, carbon dioxide, hormones, and blood ...
, regulating distant target organs. In
vertebrate Vertebrates () comprise all species of animal Animals (also called Metazoa) are multicellular eukaryotic organisms that form the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic ma ...
s, the
hypothalamus The hypothalamus (from Ancient Greek wikt:ὑπό, ὑπό, "under", and wikt:θάλαμος, θάλαμος, "chamber") is a portion of the brain that contains a number of small Nucleus (neuroanatomy), nuclei with a variety of functions. One of ...

hypothalamus
is the neural control center for all endocrine systems. In
humans Humans (''Homo sapiens'') are the most populous and widespread species In biology, a species is the basic unit of biological classification, classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species ...
, the major
endocrine gland Endocrine glands are ductless glands of the endocrine system The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating dista ...
s are the
thyroid gland The thyroid, or thyroid gland, is an endocrine gland in the neck consisting of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thyroid is located at the front of th ...

thyroid gland
and the
adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal cortex ...
s. The study of the endocrine system and its disorders is known as
endocrinology Endocrinology (from '' endocrine'' + '' -ology'') is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, ...
.


Juxtacrine

Juxtacrine signaling is a type of
cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Closed spaces * Monastic cell, a small room, hut, or cave in which a monk or religious recluse lives * Prison cell, a room used to hold peopl ...
–cell or cell–
extracellular matrix In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms, ...
signaling in
multicellular Multicellular organisms are organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual contiguous system that embodies the Life#Biology, properties of life. It is a synonym for "Out ...

multicellular
organisms that requires close contact. There are three types: # A membrane
ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electro ...
(
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabol ...

protein
,
oligosaccharide An oligosaccharide (/ˌɑlɪgoʊˈsækəˌɹaɪd/; from the Greek wikt:ὀλίγος#Ancient Greek, ὀλίγος ''olígos'', "a few", and σάκχαρ ''sácchar'', "sugar") is a carbohydrate, saccharide polymer containing a small number (typicall ...
,
lipid In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms ...
) and a
membrane protein Membrane proteins are common protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, includi ...

membrane protein
of two adjacent cells
interact Interact may refer to: * Interaction Interaction is a kind of action that occurs as two or more objects have an effect upon one another. The idea of a two-way effect is essential in the concept of interaction, as opposed to a one-way causal ef ...
. # A communicating
junction Junction may refer to: Arts and entertainment * Junction (film), ''Junction'' (film), a 2012 American film * Jjunction, a 2002 Indian film * Junction (EP), by Basement Jaxx, 2002 * Junction (manga), or ''Hot Tails'' * Junction (video game), ''Ju ...
links the intracellular compartments of two adjacent cells, allowing transit of relatively small molecules. # An
extracellular matrix In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms, ...
glycoprotein Glycoproteins are protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme ...
and a membrane protein interact. Additionally, in
unicellular A unicellular organism, also known as a single-celled organism, is an organism that consists of a single cell (biology), cell, unlike a multicellular organism that consists of multiple cells. Unicellular organisms fall into two general categories: ...
organisms such as
bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a Bacte ...
, juxtacrine signaling means interactions by membrane contact. Juxtacrine signaling has been observed for some
growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein Proteins are large biomolecules or macromolecules that a ...
s,
cytokine Cytokines are a broad and loose category of small protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of function ...
and
chemokine Chemokines (Greek ''-kinos'', movement) are a family of small cytokines, or signaling protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), residues. Pro ...
cellular signals, playing an important role in the
immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, Parasitism, parasites, and Fungus, ...

immune response
.


Receptors

Cells receive information from their neighbors through a class of proteins known as
receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ne ...
. Receptors may bind with some molecules (ligands) or may interact with physical agents like light, mechanical temperature, pressure, etc. Reception occurs when the target cell (any cell with a
receptor protein In biochemistry Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biolo ...
specific to the
signal molecule In biology, cell signaling (cell signalling in British English), or cell-cell communication, governs the basic activities of cell (biology), cells and coordinates multiple-cell actions. A signal is an entity that codes or conveys information. Biolo ...
) detects a signal, usually in the form of a small, water-soluble molecule, via binding to a receptor protein on the cell surface, or once inside the cell, the signaling molecule can bind to
intracellular receptor Intracellular receptors are receptors located inside the cell rather than on its cell membrane cell membrane vs. Prokaryotes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the ...
s, other elements, or stimulate
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates int ...

enzyme
activity (e.g. gasses), as in intracrine signaling. Signaling molecules interact with a target cell as a
ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electro ...
to
cell surface receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane cell membrane vs. Prokaryotes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and ...
s, and/or by entering into the cell through its
membrane Image:Schematic size.jpg, up150px, Schematic of size-based membrane exclusion A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Biological membr ...
or
endocytosis Endocytosis is a cellular process in which Chemical substance, substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a Vesicle (biology and chem ...

endocytosis
for
intracrine Intracrine refers to a hormone A hormone (from the Greek participle , "setting in motion") is any member of a class of signaling molecules in multicellular organisms, that are transported to distant organs to regulate physiology and / or behavi ...
signaling. This generally results in the activation of
second messenger Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intracellular signals, a non-local form or cell signaling, encompassing both first me ...
s, leading to various physiological effects. In many mammals, early
embryo An embryo is the early stage of development of a multicellular organism. In general, in organisms that Sexual reproduction, reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization and continue ...

embryo
cells exchange signals with cells of the
uterus The uterus (from Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken in the area around Rome, known as Latium. Through the power of the Ro ...

uterus
. In the human
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system The human digestive system consists of the human gastrointestinal tract, gastrointestinal tract plus the accessory or ...
,
bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a Bacte ...
exchange signals with each other and with human
epithelial Epithelium is one of the four basic types of animal Tissue (biology), tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed Cell (biology), cells with little Extr ...
and
immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual contiguous system that embodies the Life#Biolog ...
cells. For the yeast ''
Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been originally isolated from the skin of ...

Saccharomyces cerevisiae
'' during
mating In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms ...
, some cells send a
peptide Peptides (from Greek language πεπτός, ''peptós'' "digested"; derived from πέσσειν, ''péssein'' "to digest") are short chains of amino acids linked by peptide bonds. Chains of fewer than ten or fifteen amino acids are called oligopep ...
signal (mating factor
pheromone exposes Nasonov's gland (white – at tip of abdomen) releasing pheromone to entice swarm into an empty hive A pheromone (from Ancient Greek ' "to bear" and hormone) is a secreted or excreted chemical factor that triggers a social response in mem ...
s) into their environment. The mating factor peptide may bind to a cell surface receptor on other yeast cells and induce them to prepare for mating.


Cell surface receptors

Cell surface receptors play an essential role in the biological systems of single- and multi-cellular organisms and malfunction or damage to these proteins is associated with cancer, heart disease, and asthma. These trans-membrane receptors are able to transmit information from outside the cell to the inside because they when a specific ligand binds to it. There are three major types: Ion channel linked receptors,
G protein–coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related prot ...
s, and
enzyme-linked receptorAn enzyme-linked receptor, also known as a catalytic receptor, is a transmembrane receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane cell membrane vs. Prokaryote ...
s.


Ion channel linked receptors

The AMPA receptor bound to a glutamate antagonist showing the amino terminal, ligand binding, and transmembrane domain, PDB 3KG2 Ion channel linked receptors are a group of
transmembrane Image:Polytopic membrane protein.png, 400px, Schematic representation of transmembrane proteins: 1) a single transmembrane α-helix (bitopic membrane protein). 2) a polytopic transmembrane α-helical protein. 3) a polytopic transmembrane β-sheet pr ...

transmembrane
ion-channel s (typically four per channel), 2 - outer vestibule, 3 - Potassium channel#Selectivity filter, selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane. Ion channels are pore-forming membrane proteins that ...
proteins which open to allow ions such as , , , and/or to pass through the membrane in response to the binding of a chemical messenger (i.e. a
ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electro ...
), such as a
neurotransmitter A neurotransmitter is a signaling molecule In biology, cell signaling (cell signalling in British English), or cell-cell communication, governs the basic activities of cells and coordinates multiple-cell actions. A signal is an entity that ...
. When a
presynaptic neuron Chemical synapses are biological junctions through which neuron A neuron or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapse SyNAPSE is a DARPA program that aims t ...
is excited, it releases a
neurotransmitter A neurotransmitter is a signaling molecule In biology, cell signaling (cell signalling in British English), or cell-cell communication, governs the basic activities of cells and coordinates multiple-cell actions. A signal is an entity that ...
from vesicles into the
synaptic cleft Synaptic may refer to: * Synapse SyNAPSE is a DARPA program that aims to develop electronic neuromorphic machine technology, an attempt to build a new kind of cognitive computer with form, function, and architecture similar to the mammalian bra ...
. The neurotransmitter then binds to receptors located on the
postsynaptic neuron Chemical synapses are biological junctions through which neuron A neuron or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapse SyNAPSE is a DARPA program that aims t ...
. If these receptors are ligand-gated ion channels, a resulting conformational change opens the ion channels, which leads to a flow of ions across the cell membrane. This, in turn, results in either a
depolarization In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms, ...
, for an excitatory receptor response, or a hyperpolarization, for an inhibitory response. These receptor proteins are typically composed of at least two different domains: a transmembrane domain which includes the ion pore, and an extracellular domain which includes the ligand binding location (an
allosteric 300px, Allosteric regulation of an enzyme In biochemistry Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be ...

allosteric
binding site). This modularity has enabled a 'divide and conquer' approach to finding the structure of the proteins (crystallising each domain separately). The function of such receptors located at
synapse SyNAPSE is a DARPA program that aims to develop electronic neuromorphic machine technology, an attempt to build a new kind of cognitive computer with form, function, and architecture similar to the mammalian brain. Such artificial brains would ...

synapse
s is to convert the chemical signal of
presynaptic SyNAPSE is a DARPA program that aims to develop electronic neuromorphic machine technology, an attempt to build a new kind of cognitive computer with form, function, and architecture similar to the mammalian brain. Such artificial brains would be u ...
ally released neurotransmitter directly and very quickly into a
postsynaptic Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system ...
electrical signal. Many LICs are additionally modulated by
allosteric 300px, Allosteric regulation of an enzyme In biochemistry Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be ...
Ligand (biochemistry), ligands, by channel blockers, ions, or the membrane potential. LICs are classified into three superfamilies which lack evolutionary relationship: cys-loop receptors, Glutamate-gated ion channel family, ionotropic glutamate receptors and P2X purinoreceptor, ATP-gated channels.


G protein–coupled receptors

G protein-coupled receptors are a large group of protein family, evolutionarily-related proteins that are
cell surface receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane cell membrane vs. Prokaryotes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and ...
s that detect
molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecule is an electrically neutral group of two or more atoms held together by chemical bo ...

molecule
s outside the cell (biology), cell and activate cellular responses. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the
cell membrane cell membrane vs. Prokaryotes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates the interior of all cells from the out ...
seven times. Text was copied from this source, which is available under
Attribution 2.5 Generic (CC BY 2.5)
license.
Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and animals. The ligand (biochemistry), ligands that bind and activate these receptors include light-sensitive compounds, odors,
pheromone exposes Nasonov's gland (white – at tip of abdomen) releasing pheromone to entice swarm into an empty hive A pheromone (from Ancient Greek ' "to bear" and hormone) is a secreted or excreted chemical factor that triggers a social response in mem ...
s,
hormone A hormone (from the Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approximately 10.7 m ...

hormone
s, and
neurotransmitter A neurotransmitter is a signaling molecule In biology, cell signaling (cell signalling in British English), or cell-cell communication, governs the basic activities of cells and coordinates multiple-cell actions. A signal is an entity that ...
s, and vary in size from small molecules to
peptide Peptides (from Greek language πεπτός, ''peptós'' "digested"; derived from πέσσειν, ''péssein'' "to digest") are short chains of amino acids linked by peptide bonds. Chains of fewer than ten or fifteen amino acids are called oligopep ...
s to large
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabol ...

protein
s. G protein-coupled receptors are involved in many diseases. There are two principal signal transduction pathways involving the G protein-coupled receptors: cyclic adenosine monophosphate, cAMP signal pathway and phosphatidylinositol signal pathway. When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor (GEF). The GPCR can then activate an associated G protein by exchanging the guanosine diphosphate, GDP bound to the G protein for a guanosine triphosphate, GTP. The G protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gs alpha subunit, Gαs, Gi alpha subunit, Gαi/o, Gq alpha subunit, Gαq/11, G12/G13 alpha subunits, Gα12/13). G protein-coupled receptors are an important drug target and approximately 34% of all Food and Drug Administration (FDA) approved drugs target 108 members of this family. The global sales volume for these drugs is estimated to be 180 billion US dollars . It is estimated that GPCRs are targets for about 50% of drugs currently on the market, mainly due to their involvement in signaling pathways related to many diseases i.e. mental, metabolic including endocrinological disorders, immunological including viral infections, cardiovascular, inflammatory, senses disorders, and cancer. The long ago discovered association between GPCRs and many endogenous and exogenous substances, resulting in e.g. analgesia, is another dynamically developing field of pharmaceutical research.


Enzyme-linked receptors

Enzyme-linked receptors (or catalytic receptors) are transmembrane receptors that, upon activation by an extracellular Ligand (biochemistry), ligand, causes enzymatic activity on the intracellular side. Hence a catalytic receptor is an integral membrane protein possessing both Enzyme, enzymatic, catalysis, catalytic, and receptor functions. They have two important domains, an extra-cellular ligand binding domain and an intracellular domain, which has a catalytic function; and a single transmembrane helix. The signaling molecule binds to the receptor on the outside of the cell and causes a conformational change on the catalytic function located on the receptor inside the cell. Examples of the enzymatic activity include: * Receptor tyrosine kinase, as in fibroblast growth factor receptor. Most enzyme-linked receptors are of this type. * Serine/threonine-specific protein kinase, as in bone morphogenetic protein * Guanylate cyclase, as in atrial natriuretic factor receptor


Intracellular receptors


Steroid hormone receptor

Steroid hormone receptors are found in the cell nucleus, nucleus, cytosol, and also on the plasma membrane of target cells. They are generally
intracellular receptor Intracellular receptors are receptors located inside the cell rather than on its cell membrane cell membrane vs. Prokaryotes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the ...
s (typically cytoplasmic or nuclear) and initiate
signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation residue Protein phosphorylation is a reversible post-translational m ...
for steroid hormones which lead to changes in gene expression over a time period of hours to days. The best studied steroid hormone receptor (biochemistry), receptors are members of the
nuclear receptor of a heterodimer of the nuclear receptors PPAR-γ (green) and RXR-α (cyan) bound to double stranded DNA The structure of part of a DNA double helix Deoxyribonucleic acid (; DNA) is a molecule File:Pentacene on Ni(111) STM.jpg, A sca ...
subfamily 3 (NR3) that include receptors for estrogen (group NR3A) and 3-ketosteroids (group NR3C). In addition to nuclear receptors, several G protein-coupled receptors and
ion channel s (typically four per channel), 2 - outer vestibule, 3 - Potassium channel#Selectivity filter, selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane. Ion channels are pore-forming membrane proteins that ...

ion channel
s act as
cell surface receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane cell membrane vs. Prokaryotes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and ...
s for certain steroid hormones.


Signal transduction pathways

When binding to the signaling molecule, the receptor protein changes in some way and starts the process of transduction, which can occur in a single step or as a series of changes in a sequence of different molecules (called a signal transduction pathway). The molecules that compose these pathways are known as relay molecules. The multistep process of the transduction stage is often composed of the activation of proteins by addition or removal of phosphate groups or even the release of other small molecules or ions that can act as messengers. The amplifying of a signal is one of the benefits to this multiple step sequence. Other benefits include more opportunities for regulation than simpler systems do and the fine- tuning of the response, in both unicellular and multicellular organism. In some cases, receptor activation caused by ligand binding to a receptor is directly coupled to the cell's response to the ligand. For example, the neurotransmitter gamma-Aminobutyric acid, GABA can activate a cell surface receptor that is part of an
ion channel s (typically four per channel), 2 - outer vestibule, 3 - Potassium channel#Selectivity filter, selectivity filter, 4 - diameter of selectivity filter, 5 - phosphorylation site, 6 - cell membrane. Ion channels are pore-forming membrane proteins that ...

ion channel
. GABA binding to a GABAA receptor, GABAA receptor on a neuron opens a chloride-selective ion channel that is part of the receptor. GABAA receptor activation allows negatively charged chloride ions to move into the neuron, which inhibits the ability of the neuron to produce action potentials. However, for many cell surface receptors, ligand-receptor interactions are not directly linked to the cell's response. The activated receptor must first interact with other proteins inside the cell before the ultimate Physiology, physiological effect of the ligand on the cell's behavior is produced. Often, the behavior of a chain of several interacting cell proteins is altered following receptor activation. The entire set of cell changes induced by receptor activation is called a
signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation residue Protein phosphorylation is a reversible post-translational m ...
mechanism or pathway. A more complex signal transduction pathway is shown in Figure 3. This pathway involves changes of protein–protein interactions inside the cell, induced by an external signal. Many growth factors bind to receptors at the cell surface and stimulate cells to progress through the cell cycle and Cell division, divide. Several of these receptors are kinases that start to phosphorylate themselves and other proteins when binding to a ligand. This
phosphorylation In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds composed of atoms, molecules and ions: their composition, structure, properties, behavior and the changes they unde ...

phosphorylation
can generate a binding site for a different protein and thus induce protein–protein interaction. In Figure 3, the ligand (called epidermal growth factor, or EGF) binds to the receptor (called Epidermal growth factor receptor, EGFR). This activates the receptor to phosphorylate itself. The phosphorylated receptor binds to an Signal transducing adaptor protein, adaptor protein (GRB2), which couples the signal to further downstream signaling processes. For example, one of the signal transduction pathways that are activated is called the mitogen-activated protein kinase (MAPK) pathway. The signal transduction component labeled as "MAPK" in the pathway was originally called "ERK," so the pathway is called the MAPK/ERK pathway. The MAPK protein is an enzyme, a protein kinase that can attach phosphate to target proteins such as the transcription factor C-myc, MYC and, thus, alter gene transcription and, ultimately, cell cycle progression. Many cellular proteins are activated downstream of the growth factor receptors (such as EGFR) that initiate this signal transduction pathway. Some signaling transduction pathways respond differently, depending on the amount of signaling received by the cell. For instance, the hedgehog (cell signaling), hedgehog protein activates different genes, depending on the amount of hedgehog protein present. Complex multi-component signal transduction pathways provide opportunities for feedback, signal amplification, and interactions inside one cell between multiple signals and signaling pathways. A specific cellular response is the result of the transduced signal in the final stage of cell signaling. This response can essentially be any cellular activity that is present in a body. It can spur the rearrangement of the cytoskeleton, or even as catalysis by an enzyme. These three steps of cell signaling all ensure that the right cells are behaving as told, at the right time, and in synchronization with other cells and their own functions within the organism. At the end, the end of a signal pathway leads to the regulation of a cellular activity. This response can take place in the nucleus or in the cytoplasm of the cell. A majority of signaling pathways control protein synthesis by turning certain genes on and off in the nucleus. In unicellular organisms such as bacteria, signaling can be used to 'activate' peers from a Dormancy, dormant state, enhance virulence, defend against bacteriophages, etc. In
quorum sensingIn biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms, De ...
, which is also found in social insects, the multiplicity of individual signals has the potentiality to create a positive feedback loop, generating coordinated response. In this context, the signaling molecules are called autoinducers. This signaling mechanism may have been involved in evolution from unicellular to multicellular organisms. Bacteria also use contact-dependent signaling, notably to limit their growth. Signaling molecules used by multicellular organisms are often called
pheromone exposes Nasonov's gland (white – at tip of abdomen) releasing pheromone to entice swarm into an empty hive A pheromone (from Ancient Greek ' "to bear" and hormone) is a secreted or excreted chemical factor that triggers a social response in mem ...
s. They can have such purposes as alerting against danger, indicating food supply, or assisting in reproduction.


Short-term cellular responses

.


Regulating gene activity

.


Notch signaling pathway

Notch signaling pathway, Notch is a cell surface protein that functions as a receptor. Animals have a small set of genes that code for signaling proteins that interact specifically with Notch receptors and stimulate a response in cells that express Notch on their surface. Molecules that activate (or, in some cases, inhibit) receptors can be classified as hormones,
neurotransmitter A neurotransmitter is a signaling molecule In biology, cell signaling (cell signalling in British English), or cell-cell communication, governs the basic activities of cells and coordinates multiple-cell actions. A signal is an entity that ...
s, cytokines, and growth factors, in general called Ligand (biochemistry), receptor ligands. Ligand receptor interactions such as that of the Notch receptor interaction, are known to be the main interactions responsible for cell signaling mechanisms and communication. Notch signaling pathway, notch acts as a receptor for ligands that are expressed on adjacent cells. While some receptors are cell-surface proteins, others are found inside cells. For example, estrogen is a
hydrophobic In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds composed of atoms, molecules and ions: their composition, structure, properties, behavior and the changes they ...
molecule that can pass through the lipid bilayer of the
membrane Image:Schematic size.jpg, up150px, Schematic of size-based membrane exclusion A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Biological membr ...
s. As part of the endocrine system, intracellular estrogen receptors from a variety of cell types can be activated by estrogen produced in the ovary, ovaries. In the case of Notch-mediated signaling, the signal transduction mechanism can be relatively simple. As shown in Figure 2, the activation of Notch can cause the Notch protein to be altered by a protease. Part of the Notch protein is released from the cell surface membrane and takes part in gene regulation. Cell signaling research involves studying the spatial and temporal dynamics of both receptors and the components of signaling pathways that are activated by receptors in various cell types. Emerging methods for single-cell mass-spectrometry analysis promise to enable studying signal transduction with single-cell resolution. In notch signaling, direct contact between cells allows for precise control of cell differentiation (cellular), differentiation during embryonic development. In the worm ''Caenorhabditis elegans'', two cells of the developing gonad each have an equal chance of terminally differentiating or becoming a uterine precursor cell that continues to divide. The choice of which cell continues to divide is controlled by competition of cell surface signals. One cell will happen to produce more of a cell surface protein that activates the Notch #Receptors for cell signals, receptor on the adjacent cell. This activates a feedback loop or system that reduces Notch expression in the cell that will differentiate and that increases Notch on the surface of the cell that continues as a stem cell.


See also

*Scaffold protein *Biosemiotics *Molecular cellular cognition *Crosstalk (biology) *Bacterial outer membrane vesicles *Membrane vesicle trafficking *Host-pathogen interface *Retinoic acid *JAK-STAT signaling pathway *Imd pathway *Signal peptide, Localisation signal *Protein dynamics *Systems biology *Lipid signaling *Redox signaling *Cell Signaling Technology, an antibody development and production company *Netpath – A curated resource of signal transduction pathways in humans *Synthetic Biology Open Language *Nanoscale networking – leveraging biological signaling to construct ad hoc in vivo communication networks *Soliton model in neuroscience—Physical communication via sound waves in membranes


References


Further reading

* "The Inside Story of Cell Communication". ''learn.genetics.utah.edu''. Retrieved 2018-10-20. *"When Cell Communication Goes Wrong". ''learn.genetics.utah.edu''. Retrieved 2018-10-24.


External links


NCI-Nature Pathway Interaction Database
authoritative information about signaling pathways in human cells. * *
Signaling Pathways Project
cell signaling hypothesis generation knowledgebase constructed using biocurated archived transcriptomic and ChIP-Seq datasets {{Portal bar, Biology Cell signaling, Cell biology Cell communication Systems biology Human female endocrine system