EFFECTS OF A SMALL CONNEXIN 37 ISOFORM ON CELL PROLIFERATION AND CHANNEL FUNCTION

Abstract

Connexin 37 (Cx37) is a protein that regulates the formation and the development of the vascular endothelium by facilitating transmembrane signaling and intercellular communication via the formation of hemichannels (HCh) and gap junction channels (GJCh), respectively. In connexin-deficient rat insulinoma cells (Rin), Cx37 expression slows cell proliferation by phosphorylation of specific carboxyl terminus (CT) residues. Interestingly, 13 of the 21 members of the connexin gene family, including Cx37, have a conserved methionine codon at position 213 which can serve as an alternate translation start site that produces a CT-spanning translation product. Here, we created a gene construct coding for the 13 kDa alternately translated product for Cx37 which we dub Cx37-13k. We transfected it into Rin cells and show that unlike full-length Cx37, Cx37-13k is unable to arrest cell proliferation. We also demonstrate that co-expression of Cx37-13k in Cx37-expressing cells (iRin37) modifies the behavior of Cx37 HCh and GJCh. In conclusion, these data show that while Cx37-13k is insufficient in slowing Rin cell proliferation, they nevertheless lead to altered channel properties of full-length Cx37.