Abstract
Cadherins in general regulate cell-to-cell adhesion. N-cadherin is a large protein of 130 kDa with more than 700 amino acids. In cardiac myocytes, N-cadherin binds to Cx43, increasing the activation of a small GTPase, Rac1. N-cadherin binds to Cx43 and co-localizes with it at the cell membrane. Cx43 localization at the cell membrane increases Rac1 activity but does not upregulate the other small GTPases, cdc42 and RhoA. Knockdown of N-cadherin decreases Cx43 levels at the cell membrane; Cx43 and N-cadherin are both upregulated in venous leg ulcers, increasing cell motility via Rac1 activation. N-cadherin enhances gap junction formation in embryonic lens cells, presumably by increasing Cx43 expression at the cell membrane, thereby increasing intracellular communication, as assessed by a dye transfer assay. Deleting N-cadherin reduces gap junction formation. This association of cell adhesion proteins and gap junction suggests N–cadherin–Cx43 complexes are also important in the activation of cell motility and GTPases.
Keywords: Connexin43, Cadherin and Cell membrane therapy