Regulation of connexin 43-mediated gap junctional intercellular communication by Ca2+ in mouse epidermal cells is controlled by E-cadherin.

TLDR

Gap junctional intercellular communication (GJIC) in cultured mouse epidermal cells is mediated by connexin 43 and increases with higher extracellular calcium concentrations. The study aimed to determine whether E‑cadherin directly regulates calcium‑dependent GJIC in mouse epidermal cells. Researchers transfected an E‑cadherin expression vector into the low‑GJIC P3/22 cell line, generating stable clones with high E‑cadherin mRNA expression. E‑cadherin overexpression restored calcium‑dependent GJIC in P3/22 cells, demonstrating that E‑cadherin directly controls GJIC through post‑translational regulation of connexin 43.

Abstract

Gap junctional intercellular communication (GJIC) of cultured mouse epidermal cells is mediated by a gap junction protein, connexin 43, and is dependent on the calcium concentration in the medium, with higher GJIC in a high-calcium (1.2 mM) medium. In several mouse epidermal cell lines, we found a good correlation between the level of GJIC and that of immunohistochemical staining of E-cadherin, a calcium-dependent cell adhesion molecule, at cell-cell contact areas. The variant cell line P3/22 showed both low GJIC and E-cadherin protein expression in low- and high-Ca2+ media. P3/22 cells showed very low E-cadherin mRNA expression. To test directly whether E-cadherin is involved in the Ca(2+)-dependent regulation of GJIC, we transfected the E-cadherin expression vector into P3/22 cells and obtained several stable clones which expressed high levels of E-cadherin mRNA. All transfectants expressed E-cadherin molecules at cell-cell contact areas in a calcium-dependent manner. GJIC was also observed in these transfectants and was calcium dependent. These results suggest that Ca(2+)-dependent regulation of GJIC in mouse epidermal cells is directly controlled by a calcium-dependent cell adhesion molecule, E-cadherin. Furthermore, several lines of evidence suggest that GJIC control by E-cadherin involves posttranslational regulation (assembly and/or function) of the gap junction protein connexin 43.