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In biology, juxtacrine signalling (or contact-dependent signalling) is a type of cell–cell or cell–
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide struc ...
signalling in
multicellular A multicellular organism is an organism that consists of more than one cell, in contrast to unicellular organism. All species of animals, land plants and most fungi are multicellular, as are many algae, whereas a few organisms are partially un ...
organisms that requires close contact. In this type of signalling, a ligand on one surface binds to a receptor on another adjacent surface. Hence, this stands in contrast to releasing a signaling molecule by
diffusion Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...
into
extracellular space Extracellular space refers to the part of a multicellular organism outside the cells, usually taken to be outside the plasma membranes, and occupied by fluid. This is distinguished from intracellular space, which is inside the cells. The compositi ...
, the use of long-range conduits like membrane nanotubes and cytonemes (akin to 'bridges') or the use of extracellular vesicles like
exosome Exosome may refer to: * Exosome complex The exosome complex (or PM/Scl complex, often just called the exosome) is a multi-protein intracellular complex capable of degrading various types of RNA (ribonucleic acid) molecules. Exosome complexes ...
s or microvesicles (akin to 'boats'). There are three types of juxtacrine signaling: # 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 ele ...
(
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
,
oligosaccharide An oligosaccharide (/ˌɑlɪgoʊˈsækəˌɹaɪd/; from the Greek ὀλίγος ''olígos'', "a few", and σάκχαρ ''sácchar'', "sugar") is a saccharide polymer containing a small number (typically two to ten) of monosaccharides (simple sug ...
,
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids incl ...
) and 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 location. Integral membrane proteins are a permanent part of a cell membrane ...
of two adjacent cells interact. # A communicating junction links the intracellular compartments of two adjacent cells, allowing transit of relatively small molecules. # An
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide struc ...
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as g ...
and a membrane protein interact. Additionally, in unicellular organisms such as
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
, juxtacrine signaling refers to 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 or a steroid hormone. Growth factors are important for r ...
s,
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...
and
chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or Cell signaling, signaling proteins secreted by Cell (biology), cells that induce directional movement of leukocytes, as well as other cell types, including endothelial a ...
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, parasites, and fungi which could ...
. It has a critical role in development, particularly of cardiac and neural function. Other types of cell signaling include paracrine signalling and
autocrine signalling Autocrine 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 ...
. Paracrine signaling occurs over short distances, while autocrine signaling involves a cell responding to its own paracrine factors. The term "juxtacrine" was originally introduced by Anklesaria ''et al.'' (1990) to describe a possible way of signal transduction between TGF alpha and EGFR.


Cell–cell signaling

In this type of signaling, a cell places a specific
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 ele ...
on the surface of its
membrane 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. Membranes can be generally classified into synthetic membranes and biological membranes. ...
, and subsequently another cell can bind it with an appropriate
cell surface receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integr ...
or
cell adhesion molecule Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...
. An important example is the
Notch signaling pathway The Notch signaling pathway is a highly conserved cell signaling system present in most animals. Mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4. The notch receptor is a single-pass transmembr ...
, notably involved in neural development. In the Notch signaling pathway for vertebrates and ''Drosophila'', the receiving cell is told not to become neural through the binding of Delta and Notch. Within the eye of vertebrates, which cells become optic neurons and which become glial cells is regulated by Notch and its ligands.


Communicating junctions

Two adjacent cells can construct communicating conduits between their intracellular compartments:
gap junction Gap junctions are specialized intercellular connections between a multitude of animal cell-types. They directly connect the cytoplasm of two cells, which allows various molecules, ions and electrical impulses to directly pass through a regula ...
s in
animal Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...
s and plasmodesmas in
plant Plants are predominantly Photosynthesis, photosynthetic eukaryotes of the Kingdom (biology), kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all curr ...
s. Gap junctions are made of connexins in
vertebrate Vertebrates () comprise all animal taxon, taxa within the subphylum Vertebrata () (chordates with vertebral column, backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the ...
s and innexins in
invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...
s.
Electrical synapse Electricity is the set of physical phenomena associated with the presence and motion of matter that has a property of electric charge. Electricity is related to magnetism, both being part of the phenomenon of electromagnetism, as descri ...
s are electrically
conductive In physics and electrical engineering, a conductor is an object or type of material that allows the flow of charge (electric current) in one or more directions. Materials made of metal are common electrical conductors. Electric current is gen ...
gap junctions between
neuron A neuron, neurone, or nerve cell is an membrane potential#Cell excitability, electrically excitable cell (biology), cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous ...
s. Gap junctions are critical for cardiac
myocyte A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a m ...
s; mice and humans deficient in a particular gap junction protein have severe heart development defects. Plasmodesmas in plants are cytoplasmic strands that pass through cell walls and facilitate connections with adjacent cells. Plasmodesmas are highly dynamic in both strucutural modifications and biogenesis. They are able to organize cells in domains, serving as basic developmental units for plants, as well as mediate the intracellular movement of a variety of proteins and nucleic acids.


Cell–extracellular matrix signaling

The
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide struc ...
is composed of
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as g ...
s (proteins and mucopolysaccharides (glycosaminoglycan)) produced by the organism's cells. They are secreted not only to build a supportive structure but also to provide critical information on the immediate environment to nearby cells. Indeed, the cells can themselves interact by contact with extracellular matrix molecules and as such, this can be considered an indirect cell / cell communication. Cells use mainly the receptor
integrin Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...
to interact with ECM proteins. Integrins are a family of receptor proteins that integrate the extracellular and intracellular structures, allowing them to perform together. This signaling can influence the
cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA ( DNA replication) and some of its organelles, and sub ...
and cellular differentiation by directing which cells live or die, which cells proliferate, or which cells are able to exit the cell cycle and differentiate. Cellular differentiation involves a cell changing its phenotypical or functional type.


See also

*
Cell adhesion Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...
, mechanical adhesion between cells and/or the extracellular matrix * Role of cell adhesions in neural development *
Cell adhesion molecule Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...
s * Pannexin, vertebrate proteins used to form conduits between the intracellular and extracellular space *
Autocrine signalling Autocrine 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 ...
* Paracrine signalling *
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 distant target organs. In vertebrates, the hypothalamus is the neur ...


References


External links


"Autocrine versus juxtacrine signaling modes"
- illustration at sysbio.org {{Cell signaling Cell signaling