13.10: Cadherins - Biology

13.10: Cadherins - Biology

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The cadherin superfamily is comprised of the desmogleins (of which 4 have been identified in humans) and desmocollins (3 in humans), the cadherins (>20), and the protocadherins (~20) as well as other related proteins. They share structural similarity and a dependence on Ca2+ for adhesive activity, and they can be found in most tissues, and for that matter, most metazoan species. Cadherins are single-transmembrane modular proteins. On the outside of the cell, the cadherin has five domains of similar but not identical structure. It was originally thought that Ca2+ was used between cadherins to mediate adhesion, but it is now clear that Ca2+ is bound in between each extracellular domain, apparently coordinating them into a more rigid structure. Cadherins can also act in cis, i.e. cadherins from the same cell can form dimers. This property allows a patch of cadherin adhesions such as a desmosome to “zipper” together into very strong clusters.

The cytoplasmic domain of cadherins characteristically binds to a family of proteins called the catenins, and this binding can be regulated by phosphorylation of the cadherin. The most common catenins are a and β, usually with the β-catenin acting as intermediary between cadherin and α-catenin, and the α-catenin linking them to the actin microfilaments. This kind of arrangement is found in both cells that are motile, crawling over other cells that are expressing cadherin, as well as stationary cells. Although this is not the arrangement in desmosomes, the desmosomal plaque protein plakoglobin is a member of the catenin family.

The primary binding site for cadherins appears to be the N-terminal domain (most distal extracellular), although there is evidence that as many as three domains can be involved. Cadherins mostly bind homophilically (E-cadherin binds E-cadherin on another cell, but not P-cadherin), although some cadherins can bind heterophilically (e.g. N-cadherin can bind to either N-cadherin or E-cadherin). Incidentally, these three, E- cadherin (epithelial), N-cadherin (neural), and P-cadherin (placental) are the best-studied cadherins. Both E- and P-cadherins are important in early embryonic development, while N-cadherin has been studied in the context of axon guidance in the developing nervous system. E-cadherin is also a target of scrutiny because it is also important in the metastasis of cancer. In order for a cancer cell to break from the initial tumor, it must downregulate its adhesion to neighboring cells before migrating elsewhere. This is known as the epithelial-mesenchymal transition and is accompanied by decreased E-cadherin expression.

With the patch of cadherin interactions, the adherens junction (Figure (PageIndex{13})) looks very similar to the desmosome (Figure (PageIndex{12})). Adherens junctions serve some of the same purposes as desmosomes: providing connectivity to neighboring cells, and reinforcing and shaping the cells. However, adherens junctions are mostly localized near the apical surface of epithelial cells, and instead of intermediate filaments, they are connected to actin microfilaments that form a circumferential belt that produce tension and shaping forces in conjunction with myosins that associate with it.

Watch the video: Single-Cell Biology of Barrier Tissues and Covid-19. José Ordovas-Montañes (August 2022).