Cell junctions (or intercellular bridges
) are a class of cellular structures consisting of
multiprotein complexes
Protein quaternary structure is the fourth (and highest) classification level of protein structure. Protein quaternary structure refers to the structure of proteins which are themselves composed of two or more smaller protein chains (also refe ...
that provide contact or adhesion between neighboring
cells or between a cell and 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 stru ...
in animals. They also maintain the paracellular barrier of
epithelia
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
and control
paracellular transport
Paracellular transport refers to the transfer of substances across an epithelium by passing through the intercellular space ''between'' the cells. It is in contrast to transcellular transport, where the substances travel ''through'' the cell, pass ...
. Cell junctions are especially abundant in epithelial tissues. Combined with
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 and
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 stru ...
, cell junctions help hold
animal cells
The cell is the basic structural and functional unit of life forms. Every cell consists of a cytoplasm enclosed within a membrane, and contains many biomolecules such as proteins, DNA and RNA, as well as many small molecules of nutrients an ...
together.
Cell junctions are also especially important in enabling communication between neighboring cells via specialized protein complexes called
communicating (gap) junctions. Cell junctions are also important in reducing stress placed upon cells.
In plants, similar communication channels are known as
plasmodesmata
Plasmodesmata (singular: plasmodesma) are microscopic channels which traverse the cell walls of plant cells and some algal cells, enabling transport and communication between them. Plasmodesmata evolved independently in several lineages, and spec ...
, and in
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
they are called
septal pores.
Types
![Cell junction simplified en](https://upload.wikimedia.org/wikipedia/commons/b/b9/Cell_junction_simplified_en.svg)
In
vertebrate
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...
s, there are three major types of cell junction:
*
Adherens junction
Adherens junctions (or zonula adherens, intermediate junction, or "belt desmosome") are protein complexes that occur at cell–cell junctions, cell–matrix junctions in epithelial and endothelial tissues, usually more basal than tight junctions. ...
s,
desmosome
A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adh ...
s and
hemidesmosome
Hemidesmosomes are very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matrix. They are similar in form to desmosomes when visualized by electron microscopy, however, desmosomes attach t ...
s (anchoring junctions)
*
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 regulate ...
s (communicating junction)
*
Tight junction
Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...
s (occluding junctions)
Invertebrates
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 ...
have several other types of specific junctions, for example
septate junctions or the
''C. elegans'' apical junction. In multicellular
plant
Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclud ...
s, the structural functions of cell junctions are instead provided for by
cell wall
A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...
s. The analogues of communicative cell junctions in plants are called
plasmodesmata
Plasmodesmata (singular: plasmodesma) are microscopic channels which traverse the cell walls of plant cells and some algal cells, enabling transport and communication between them. Plasmodesmata evolved independently in several lineages, and spec ...
.
Anchoring junctions
Cells within tissues and organs must be anchored to one another and attached to components of 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 stru ...
. Cells have developed several types of junctional complexes to serve these functions, and in each case, anchoring proteins extend through the plasma membrane to link cytoskeletal proteins in one cell to cytoskeletal proteins in neighboring cells as well as to proteins in the extracellular matrix.
Three types of anchoring junctions are observed, and differ from one another in the cytoskeletal protein anchor as well as the transmembrane linker protein that extends through the membrane:
Anchoring-type junctions not only hold cells together but provide tissues with structural cohesion. These junctions are most abundant in tissues that are subject to constant mechanical stress such as skin and heart.
Desmosomes
![Desmosome Cell Junction](https://upload.wikimedia.org/wikipedia/commons/7/7b/Desmosome_Cell_Junction.png)
Desmosomes, also termed as maculae adherentes, can be visualized as rivets through the
plasma membrane
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 and protects the interior of all cells from the outside environment (t ...
of adjacent cells.
Intermediate filaments
Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate ''Branchiostoma''.
Intermedia ...
composed of
keratin
Keratin () is one of a family of structural fibrous proteins also known as ''scleroproteins''. Alpha-keratin (α-keratin) is a type of keratin found in vertebrates. It is the key structural material making up scales, hair, nails, feathers, ho ...
or
desmin
Desmin is a protein that in humans is encoded by the ''DES'' gene. Desmin is a muscle-specific, type III intermediate filament that integrates the sarcolemma, Z disk, and nuclear membrane in sarcomeres and regulates sarcomere architecture.
Str ...
are attached to membrane-associated attachment proteins that form a dense plaque on the cytoplasmic face of the membrane. Cadherin molecules form the actual anchor by attaching to the cytoplasmic plaque, extending through the membrane and binding strongly to cadherins coming through the membrane of the adjacent cell.
Hemidesmosomes
Hemidesmosomes form rivet-like links between cytoskeleton and extracellular matrix components such as the
basal lamina
The basal lamina is a layer of extracellular matrix secreted by the epithelial cells, on which the epithelium sits. It is often incorrectly referred to as the basement membrane, though it does constitute a portion of the basement membrane. The ba ...
e that underlie epithelia. Like desmosomes, they tie to intermediate filaments in the cytoplasm, but in contrast to desmosomes, their transmembrane anchors are integrins rather than cadherins.
Adherens junctions
Adherens junctions share the characteristic of anchoring cells through their cytoplasmic
actin filaments
Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other pr ...
. Similarly to desmosomes and hemidesmosomes, their transmembrane anchors are composed of cadherins in those that anchor to other cells and integrins (focal adhesion) in those that anchor to extracellular matrix. There is considerable
morphologic diversity among adherens junctions. Those that tie cells to one another are seen as isolated streaks or spots, or as bands that completely encircle the cell. The band-type of adherens junctions is associated with bundles of actin filaments that also encircle the cell just below the plasma membrane. Spot-like adherens junctions called
focal adhesion
In cell biology, focal adhesions (also cell–matrix adhesions or FAs) are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell. More ...
s help cells adhere to extracellular matrix. The cytoskeletal actin filaments that tie into adherens junctions are contractile proteins and in addition to providing an anchoring function, adherens junctions are thought to participate in folding and bending of epithelial cell sheets. Thinking of the bands of actin filaments as being similar to 'drawstrings' allows one to envision how contraction of the bands within a group of cells would distort the sheet into interesting patterns.
Communicating (gap) junctions
Communicating junctions, or
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 regulate ...
s allow for direct chemical communication between adjacent cellular cytoplasm through diffusion without contact with the extracellular fluid.
This is possible due to six
connexin
Connexins (Cx)TC# 1.A.24, or gap junction proteins, are structurally related transmembrane proteins that assemble to form vertebrate gap junctions. An entirely different family of proteins, the innexins, form gap junctions in invertebrates. Ea ...
proteins interacting to form a cylinder with a pore in the centre called a
connexon
In biology, a connexon, also known as a connexin hemichannel, is an assembly of six proteins called connexins that form the pore for a gap junction between the cytoplasm of two adjacent cells. This channel allows for bidirectional flow of ions and ...
.
The connexon complexes stretches across the cell membrane and when two adjacent cell connexons interact, they form a complete gap junction channel.
Connexon pores vary in size, polarity and therefore can be specific depending on the connexin proteins that constitute each individual connexon.
Whilst variation in gap junction channels do occur, their structure remains relatively standard, and this interaction ensures efficient communication without the escape of molecules or ions to the extracellular fluid.
Gap junctions play vital roles in the human body,
including their role in the uniform contractile of the
heart muscle
Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle tha ...
.
They are also relevant in signal transfers in the
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
, and their absence shows a decreased cell density in the brain.
Retinal and
skin cells
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different de ...
are also dependent on gap junctions in cell differentiation and proliferation.
Tight junctions
Found in vertebrate
epithelia
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
, tight junctions act as barriers that regulate the movement of water and solutes between epithelial layers. Tight junctions are classified as a
paracellular
Paracellular transport refers to the transfer of substances across an epithelium by passing through the intercellular space ''between'' the cells. It is in contrast to transcellular transport, where the substances travel ''through'' the cell, pass ...
barrier which is defined as not having directional discrimination; however, movement of the solute is largely dependent upon size and charge. There is evidence to suggest that the structures in which solutes pass through are somewhat like pores.
Physiological pH plays a part in the selectivity of solutes passing through tight junctions with most tight junctions being slightly selective for cations. Tight junctions present in different types of epithelia are selective for solutes of differing size, charge, and polarity.
Proteins
There have been approximately 40 proteins identified to be involved in tight junctions. These proteins can be classified into four major categories;
scaffolding proteins, signalling proteins,
regulation proteins, and
transmembrane protein
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...
s.
=Roles
=
* Scaffolding proteins – organise the transmembrane proteins, couple transmembrane proteins to other cytoplasmic proteins as well as to actin filaments.
* Signaling proteins – involved in junctions assembly, barrier regulation, and gene transcription.
* Regulation proteins – regulate membrane vesicle targeting.
* Transmembrane proteins – including
junctional adhesion molecule
A junctional adhesion molecule (JAM) is a protein that is a member of the immunoglobulin superfamily, and is expressed in a variety of different tissues, such as leukocytes, platelets, and epithelial and endothelial cells. They have been shown to ...
,
occludin
Occludin is an enzyme ( EC 1.6) that oxidizes NADH. It was first identified in epithelial cells as a 65 kDa integral plasma-membrane protein localized at the tight junctions. Together with Claudins, and zonula occludens-1 (ZO-1), occludin has bee ...
, and
claudin
Claudins are a family of proteins which, along with occludin, are the most important components of the tight junctions ( zonulae occludentes). Tight junctions establish the paracellular barrier that controls the flow of molecules in the interce ...
.
It is believed that claudin is the protein molecule responsible for the selective permeability between epithelial layers.
A three-dimensional image is still yet to be achieved and as such specific information about the function of tight junctions is yet to be determined.
Tricellular junctions
Tricellular junctions seal epithelia at the corners of three cells. Due to the geometry of three-cell vertices, the sealing of the cells at these sites requires a specific junctional organization, different from those in bicellular junctions. In vertebrates, components tricellular junctions are tricellulin and lipolysis-stimulated lipoprotein receptors. In invertebrates, the components are gliotactin and anakonda.
![Epithelium TCJ](https://upload.wikimedia.org/wikipedia/commons/0/0d/Epithelium_TCJ.png)
Tricellular junctions are also implicated in the regulation of cytoskeletal organization and cell divisions. In particular they ensure that cells divide according to the
Hertwig rule. In some Drosophila epithelia, during cell divisions tricellular junctions establish physical contact with
spindle apparatus
In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a pr ...
through astral microtubules. Tricellular junctions exert a pulling force on the spindle apparatus and serve as a geometrical clues to determine orientation of cell divisions.
Cell junction molecules
The molecules responsible for creating cell junctions include various
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. There are four main types:
selectins
The selectins (cluster of differentiation 62 or CD62) are a family of cell adhesion molecules (or CAMs). All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus a ...
,
cadherins
Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to allow cells to adhere to each other . Cadherins are a class of type-1 transmembrane proteins, ...
,
integrins
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, ...
, and the
immunoglobulin superfamily
The immunoglobulin superfamily (IgSF) is a large protein superfamily of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily ba ...
.
Selectins
The selectins (cluster of differentiation 62 or CD62) are a family of cell adhesion molecules (or CAMs). All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus a ...
are cell adhesion molecules that play an important role in the initiation of inflammatory processes.
The functional capacity of selectin is limited to leukocyte collaborations with vascular endothelium. There are three types of selectins found in humans; L-selectin, P-selectin and E-selectin. L-selectin deals with lymphocytes, monocytes and neutrophils, P-selectin deals with platelets and endothelium and E-selectin deals only with endothelium. They have extracellular regions made up of an amino-terminal lectin domain, attached to a carbohydrate ligand, growth factor-like domain, and short repeat units (numbered circles) that match the complementary binding protein domains.
Cadherins
Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to allow cells to adhere to each other . Cadherins are a class of type-1 transmembrane proteins, ...
are calcium-dependent adhesion molecules. Cadherins are extremely important in the process of
morphogenesis
Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of devel ...
–
fetal development
Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal devel ...
. Together with an alpha-beta
catenin
Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells. The first two catenins that were identified became known as α-catenin and β-catenin. α-Catenin can bind to β-catenin and can also bind ...
complex, the cadherin can bind to the microfilaments of the cytoskeleton of the cell. This allows for homophilic cell–cell adhesion.
The
β-catenin
Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcripti ...
–
α-catenin
Alpha-catenin functions as the primary protein link between cadherins and the actin cytoskeleton. It has been reported that the actin binding proteins vinculin and alpha-actinin can bind to alpha-catenin. It has been suggested that alpha-caten ...
linked complex at the adherens junctions allows for the formation of a dynamic link to the actin cytoskeleton.
Integrins
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, ...
act as adhesion receptors, transporting signals across the plasma membrane in multiple directions. These molecules are an invaluable part of cellular communication, as a single ligand can be used for many integrins. Unfortunately these molecules still have a long way to go in the ways of research.
Immunoglobulin superfamily
The immunoglobulin superfamily (IgSF) is a large protein superfamily of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily ba ...
are a group of calcium independent proteins capable of homophilic and heterophilic adhesion. Homophilic adhesion involves the immunoglobulin-like domains on the cell surface binding to the immunoglobulin-like domains on an opposing cell’s surface while heterophilic adhesion refers to the binding of the immunoglobulin-like domains to integrins and carbohydrates instead.
Cell adhesion is a vital component of the body. Loss of this adhesion effects cell structure, cellular functioning and communication with other cells and the extracellular matrix and can lead to severe health issues and diseases.
References
External links
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{{Authority control
Cell anatomy
Cell communication
Cell signaling