Connexin 26 gap junction coupling selectively contributes to reduced adhesivity and increased cell migration

Abstract

Gap junction proteins (connexins) have critical effects on cell motility in many systems, from migration of neural crest cells to promotion of metastatic invasiveness, Here we show that expression of Cx26 in HeLa cells specifically enhances cell motility in scrape wounding and sparse culture models. This effect is dependent on gap junction channels and is isotype specific (Cx26 enhances motility, while Cx43 does not. Cx32 has an intermediate effect). The increased motility is associated with reduced cell adhesiveness, caused by loss of N-cadherin protein and RNA at the wound edge. This in turn causes a redistribution of N-cadherin binding proteins (p120catenin and β-catenin) to the cytosol and nucleus, respectively. The former activates Rac-1, which mediates cytoskeletal rearrangements needed for filopod extension. The latter is associated with increased expression of urokinase plasminogen activating receptor (an activator of extracellular proteases) and secretion of extracellular matrix components like collagen. While these effects were dependent on Cx26 coupling of the cells, they are not mediated by the same signal (i.e. cAMP) by which Cx26 has been shown to suppress proliferation in the same system.