Connexin 50 Functions as an Adhesive Molecule and Promotes Lens Cell Differentiation

Connexinsplay essential roles in lens homeostasis and development. Here, we identified a new role for Cx50 that mediates cell- cell adhesionfunction. Cx50 enhanced the adhesivecapability of AQP0. Interestingly, the expression of Cx50 alone promoted cell adhesionat a comparable level to AQP0; however, this cell adhesivefunction was not observed with other lens connexins, Cx43 and Cx46. Moreover, the adhesiveproperty occurred in both homotypic with Cx50 expressed in both pairing cells and heterotypic with Cx50 in only one pairing cell, and this function appears to be unrelated to its role in forming gap junctionchannels. Cx50 KO lenses exhibited increased intercellular spaces between lens fiber cells. The second extracellular loop domain (E2) is primarily responsible for this adhesivefunction. Treatment with a fusion protein containing E2 domain inhibited cell adhesion. Furthermore, disruption of cell adhesionby the E2 domains impaired primary lens cell differentiation. Five critical amino acid residues in the E2 domain primarily are involved in cell adhesivefunction as well as lens epithelial-fiber differentiation. Together, these results suggest that in addition to forming gap junctionchannels, Cx50 acts as an adhesivemolecule that is critical in maintaining lens fiber integrity and epithelial-fiber differentiation.