Differential regulation of Connexin50 and Connexin46 by PI3K signaling

Gap junction channels can modify their activity in response to cell signaling pathways. Here, we demonstrate that Connexin50 (Cx50) coupling, but not Connexin46 (Cx46), increased when co-expressed with a constitutively active p110 alpha subunit of PI3K in Xenopus oocytes. In addition, inhibition of PI3K signaling by blocking p110 alpha, or Akt, significantly decreased gap junctional conductance in Cx50 transfected HeLa cells, with no effect on Cx46. Alterations in coupling levels were not a result of reduced Cx50 unitary conductance, suggesting that changes in the number of active channels were responsible. These data indicate that Cx50 is specifically regulated by the PI3K signaling pathway. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.