Gap junctions are membrane channels between cells that allow the exchange of substances from the cytoplasm of one cell directly to the cytoplasm of an adjacent cell. Substances exchanged include small molecules, substrates, and metabolites.
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 signaling molecules. The connexon is the hemichannel supplied by a cell on one side of the junction; two connexons from opposing cells normally come together to form the complete intercellular gap junction channel. In some cells, the hemichannel itself is active as a conduit between the cytoplasm and the extracellular space, allowing the transference of ions and small molecules lower than 1-2 KDa. Little is known about this function of connexons besides the new evidence suggesting their key role in intracellular signaling. In still other cells connexons have been shown to occur in mitochondrial membranes and appear to play a role in heart ischaemia.
Connexins (Cx), or gap junction proteins, are structurally related transmembrane proteins that assemble to form vertebrate gap junctions. An entirely different family of proteins, the innexins, forms gap junctions in invertebrates. Each gap junction is composed of two hemichannels, or connexons, which consist of homo- or heterohexameric arrays of connexins, and the connexon in one plasma membrane docks end-to-end with a connexon in the membrane of a closely opposed cell. The hemichannel is made of six connexin subunits, each of which consist of four transmembrane segments. Gap junctions are essential for many physiological processes, such as the coordinated depolarization of cardiac muscle, proper embryonic development, and the conducted response in microvasculature. Connexins also have non-channel dependant functions relating to cytoskeleton and cell migration. For these reasons, mutations in connexin-encoding genes can lead to functional and developmental abnormalities.
Cell junctions or junctional complexes are a class of cellular structures consisting of multiprotein complexes that provide contact or adhesion between neighboring cells or between a cell and the extracellular matrix in animals. They also maintain the paracellular barrier of epithelia and control paracellular transport. Cell junctions are especially abundant in epithelial tissues. Combined with cell adhesion molecules and extracellular matrix, cell junctions help hold animal cells together.
In biology, juxtracrine signalling is a type of cell–cell or cell–extracellular matrix signalling in multicellular 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 into extracellular space, the use of long-range conduits like membrane nanotubes and cytonemes or the use of extracellular vesicles like exosomes or microvesicles. There are three types of juxtracrine signaling:
- A membrane-bound ligand and a membrane protein 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 glycoprotein and a membrane protein interact.
ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by rhinovirus as a receptor for entry into respiratory epithelium.
Integrin, alpha L , also known as ITGAL, is a protein that in humans is encoded by the ITGAL gene. CD11a functions in the immune system. It is involved in cellular adhesion and costimulatory signaling. It is the target of the drug efalizumab.
Pannexins are a family of vertebrate proteins identified by their homology to the invertebrate innexins. While innexins are responsible for forming gap junctions in invertebrates, the pannexins have been shown to predominantly exist as large transmembrane channels connecting the intracellular and extracellular space, allowing the passage of ions and small molecules between these compartments.
Gap junction alpha-1 protein (GJA1), also known as connexin 43 (Cx43), is a protein that in humans is encoded by the GJA1 gene on chromosome 6. As a connexin, GJA1 is a component of gap junctions, which allow for gap junction intercellular communication (GJIC) between cells to regulate cell death, proliferation, and differentiation. As a result of its function, GJA1 is implicated in many biological processes, including muscle contraction, embryonic development, inflammation, and spermatogenesis, as well as diseases, including oculodentodigital dysplasia (ODDD), heart malformations, and cancers.
Gap junction beta-2 protein (GJB2), also known as connexin 26 (Cx26) — is a protein that in humans is encoded by the GJB2 gene.
Intercellular adhesion molecule 3 (ICAM3) also known as CD50, is a protein that in humans is encoded by the ICAM3 gene. The protein is constitutively expressed on the surface of leukocytes, which are also called white blood cells and are part of the immune system. ICAM3 mediates adhesion between cells by binding to specific integrin receptors. It plays an important role in the immune cell response through its facilitation of interactions between T cells and dendritic cells, which allows for T cell activation. ICAM3 also mediates the clearance of cells undergoing apoptosis by attracting and binding macrophages, a type of cell that breaks down infected or dying cells through a process known as phagocytosis, to apoptotic cells.
Gap junction alpha-5 protein (GJA5), also known as connexin 40 (Cx40) — is a protein that in humans is encoded by the GJA5 gene.
Gap junction beta-6 protein (GJB6), also known as connexin 30 (Cx30) — is a protein that in humans is encoded by the GJB6 gene. Connexin 30 (Cx30) is one of several gap junction proteins expressed in the inner ear. Mutations in gap junction genes have been found to lead to both syndromic and nonsyndromic deafness. Mutations in this gene are associated with Clouston syndrome.
Gap junction gamma-1 protein (GJC1), also known as gap junction alpha-7 protein (GJA7) and connexin 45 (Cx45) — is a protein that in humans is encoded by the GJC1 gene.
Cell–cell interaction refers to the direct interactions between cell surfaces that play a crucial role in the development and function of multicellular organisms. These interactions allow cells to communicate with each other in response to changes in their microenvironment. This ability to send and receive signals is essential for the survival of the cell. Interactions between cells can be stable such as those made through cell junctions. These junctions are involved in the communication and organization of cells within a particular tissue. Others are transient or temporary such as those between cells of the immune system or the interactions involved in tissue inflammation. These types of intercellular interactions are distinguished from other types such as those between cells and the extracellular matrix. The loss of communication between cells can result in uncontrollable cell growth and cancer.
Gap junction delta-2 protein (GJD2), also known as connexin-36 (Cx36) or gap junction alpha-9 protein (GJA9), is a protein that in humans is encoded by the GJD2 gene.
Gap junction beta-5 protein (GJB5), also known as connexin-31.1 (Cx31.1), is a protein that in humans is encoded by the GJB5 gene.
Gap junction alpha-10 protein, also known as connexin-62 (Cx62), is a protein that in humans is encoded by the GJA10 gene.
An intercellular cleft is a channel between two cells through which molecules may travel and gap junctions and tight junctions may be present. Most notably, intercellular clefts are often found between epithelial cells and the endothelium of blood vessels and lymphatic vessels, also helping to form the blood-nerve barrier surrounding nerves. Intercellular clefts are important for allowing the transportation of fluids and small solute matter through the endothelium.
Intercellular communication (ICC) refers to the various ways and structures that biological cells use to communicate with each other directly or through their environment. Often the environment has been thought of as the extracellular spaces within an animal. More broadly cells may also communicate with other animals, either of their own group or species, or other species in the wider ecosystem. Different types of cells use different proteins and mechanisms to communicate with one another using extracellular signalling molecules or electric fluctuations which could be likened to an intercellular ethernet. Components of each type of intercellular communication may be involved in more than one type of communication making attempts at clearly separating the types of communication listed somewhat futile. Broadly speaking, intercellular communication may be categorized as being within a single animal, or between an animal and other animals in the ecosystem in which it lives. In this article intercellular communication has been further collated into various areas of research rather than by functional or structural characteristics.
