Cell junction, otherwise known as intercellular bridge, is a structural formation that exists between cells of a multicellular organism or between cells and a basement membrane or an extracellular matrix. It is made up of protein complexes that enables the cell to cell contact and which also provides the medium through which these cells communicate. Moreover, it is this cell to cell contact which forms a uniform layer of cells which is the basis of epithelial surfaces. As a result, cell junctions are abundantly present in epithelial tissues where they serve to control paracellular transport. Of note is that these protein complexes, also known as communicating junctions, are the main enablers of communication between cells.
The three major types of cell junction that exists are the communicating junctions, the occluding junctions, and the anchoring junctions. The communicating junctions, also known as the gap junctions, allows for cell to cell communication which may be in the form of electrical currents, ions, chemical substances or even small molecules. This communication occurs between the cytoplasm of these cells (Mescher, 2013). The cytoplasm of these cells are connected by two hemichannels or connexons. These hemichannels form the gap junction and run through the intercellular space from one cell to the other. For vertebrates, these hemichannels are either heterohexamers or homohexamers. When the hemichannels are homohexamers, the gap junction is called homotypic whereas the gap junction is referred to as heteromeric when the hemichannels are not similar. The composition of the gap junctions is believed to affect the function of the junctions. The hemichannels are made up of structural units called connexins; six connexins make a single connexon which is the hemichannel (Young et al., 2013). The hemichannel is structured in a way that the small molecules that are passing through them are not lost in the intercellular space. Moreover, the chemical interaction between the cells is through the transmission of second messengers, for example, inositol triphosphate and calcium. Generally, hemichannels allow for movement of molecules smaller than 485 Daltons. Different functions have been associated with gap junctions including their functions as tumor suppressor genes ( for example Cx43), electrical and chemical coupling between cells, electrical and chemical exchange and adhesive properties.
For invertebrates, however, the gap junctions are made up of proteins that are from the innexin family of proteins. The innexins do not bear any sequential resemblance to the connexins even though they both form gap junctions (albeit of different classes of organisms).
The anchoring junctions help in the physical anchorage of cells to one another or to the extracellular matrix .These anchoring proteins stretch through the plasmalemma to link cytoskeleton of cells .The three subtypes of anchoring proteins are desmosomes, hemidesmosomes and adherent junctions (Mescher, 2013). Desmosome, or macula adherents as they are also known, are mainly for the adhesion of one cell to another. Desmosomes are abundantly found in tissues that undergo physical stress such as the heart muscle and muscles of the bladder and the gastrointestinal system. Structurally, desmosomes are made up of desmosome-intermediate filament complexes which is subdivided into three parts. The three parts are the extracellular region, the dense outer plaque and the inner dense plaque (Young et al., 2013). The desmosome intermediate complex consists of interaction between cadherin proteins, linker proteins, and keratin intermediate filaments. The extracellular region is made up of cadherin proteins desmoglein and desmocollin which are bound together strongly by extracellular calcium (Young et al., 2013). As a result, all the five extracellular domains of both the desmoglein and desmocollin have motifs for calcium binding. Desmoglein and desmocollin bind heterophilicaly near the N termini in the extracellular space.
The dense outer plaque of the desmosomes are made up of the intracellular endings of the desmoglein and desmocollin, desmoplakin , plakoglobin, and plakophilin. Plakoglobin and plakophilin help in the attachment to proteins of the cell membrane and filaments that are intracellular. Moreover, they help maintain the structure of desmoplakin and keratin within the desmosome.
The inner dense plaque consists of desmoplakin and keratin intermediate filaments. The C terminus ends of the desmoplakin are attached to the keratin intermediate filaments. The desmoplakin serves to connect desmoglein and desmocollin to keratin filaments.
The hemidesmosomes are different from the desmosomes in that their transmembrane anchors are integrins and not cadherins. Hemidesmosomes connect the cells to extracellular matrices. They are majorly found in epithelial tissues where they connect the basal epithelial cells to the basal lamina. Hemidesmosomes are either type 1 or type 2. Both types are made up of integrins and pectins (Gartner & Hiatt, 2006). However, type 2 hemidesmosomes do not have BP antigens which are present in the type 1 hemidesmosomes. The structure of the hemidesmosomes is such that integrin part is made up of two subunit dimers, alpha, and beta. The beta subunit binds fibronectin and calcium while the alpha subunit serves to bind BP 180, CD 151 and laminin 322. Binding of integrins to plectins associates it with keratin intermediate filaments found in the cytoskeleton. Plectins link hemidesmosomes to keratin.
The adherent junctions anchor cells through actin filaments found in the cytoplasm. Like desmosomes and hemidesmosomes, they are made up of cadherins when mediating cell to cell anchorage and made up of integrins when mediating cell anchorage to the extracellular matrices. Adherent junctions can either be zonula adherens or adhesion plaques. Zonula adherens surround the whole cell while adhesion plaques appear as isolated points of attachment to the extracellular matrix. The structure of the adherent junctions is that they are made up of four proteins which are cadherins, delta catenins, gamma catenins, and alpha catenins.
Having broadly discussed communicating junctions and anchoring junctions, the third type of cell junctions is the occluding junctions. The occluding junctions are also known as tight junctions. As the name suggests, occluding junctions serves to restrict the movement of molecules paracellularly hence the description as paracellular barriers. Of note is that invertebrates do not have tight junctions but instead have septate junctions. The structure of the tight junctions is that they are made up of a network of branching strands. These strands serve to seal and each strand functions separately from the others. The functionality of the occluding junctions in acting as a paracellular barrier is largely dependent on the number of strands that are present in the junction. A single strand is made of proteins that are transmembrane and which are held in plasma membranes. The extracellular domains of these strands are connected to one another directly. Claudins and occludins are the proteins that make up the tight junctions. They, however, associate with several other proteins to complete the integrity of the tight junctions. Of note is that these occluding junctions connect the cytoskeleton of cells that are adjacent through the strands.
Occluding junctions serves a number of functions. These functions are not only important but are also very vital. These functions include holding the cells together. This is important as it helps in maintaining the integrity of the epithelial surface. Occluding junctions also have barrier functions. Barrier functions can be either protective or functional. Protective barrier , as the name suggests, restricts material transport paracellularly. Tight junctions help preserve and maintain the transcellular transport by maintaining the polarity of cells. This is achieved by preventing lateral movements of proteins between the apical and basal surfaces thus allowing for the preservation of the specialized functions of each surface. Tight junctions also augment the transport of materials through diffusion and active transport as tight junction restricts the movement of these materials through the space that exists between adjacent plasma membranes of adjacent cells.
Conclusion
Finally regarding tight junctions are the proteins involved. Occludins and claudins earlier mentioned are transmembrane proteins. Others are scaffolding proteins, signaling proteins and regulation proteins.
References
Gartner, L. P., & Hiatt, J. L. (2006). Color textbook of histology e-book. Elsevier Health Sciences.
Mescher, A. L. (2013). Junqueira's basic histology: text and atlas. Mcgraw-hill.
Young, B., Woodford, P., & O'Dowd, G. (2013). Wheater's Functional Histology E-Book: A Text and Colour Atlas. Elsevier Health Sciences.
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