classical cadherins
Definition: Classical cadherins are a family of single-span transmembrane-domain glycoproteins that function as specific cell-cell adhesion molecules.
Functions
Cadherin-mediated cell-cell adhesion is accomplished by homophilic protein-protein interactions between two cadherin molecules at the surface of the respective cells. This interaction is thought to be mediated by interactions between the histidine-alanine-valine (HAV) domains and between tryptophan residues and hydrophobic pockets in the most amino-terminal cadherin domains.
Individual cadherin molecules form groups and interact through their tips in a highly flexible manner. Cadherins show an exquisite specificity in their homophilic interactions by almost exclusively binding the same type of cadherin on another cell.
The intracellular domain of classical cadherins (which is lacking in non-classical cadherins and protocadherins) interacts with various catenin proteins to form the cytoplasmic cell-adhesion complex (CCC).
Interactions with catenins (CTTNs)
beta-catenin (CTNNB1) and gamma-catenin (JUP) (also known as plakoglobin) bind to the same conserved site at the carboxyl termini of classical cadherins in a mutually exclusive way, whereas another catenin, p120-catenin, interacts with several sites in the cytoplasmic tail, including the juxtamembrane region.
beta-catenin (CTNNB1) and gamma-catenin (JUP) bind directly to alpha-catenin (CTNNAs), which links the cytoplasmic cell-adhesion complex (CCC) to the actin cytoskeleton.
Without an intact cytoplasmic cell-adhesion complex (CCC), cadherin-mediated strong cell-cell adhesion is compromised and, conversely, without cell-cell adhesion the CCC will not form.
Recent detailed analysis of the potential protein-protein interaction partners of the cytoplasmic tail of cadherins and those of catenins has revealed a large number of additional interaction partners that also link the cytoplasmic cell-adhesion complex (CCC) to the microtubule network and to several signalling molecules.
Cell-to-cell interactions mediated by cadherins and catenins play a major role in regulating cell motility, proliferation, and differentiation and account for the inhibition of cell proliferation that occurs when cultured normal cells contact each other ("contact inhibition").
See also
cadherins superfamily (CDHs)