Differential regulation of Connexin50 and Connexin46 by PI3K signaling

FEBS Lett. 2015 May 22;589(12):1340-5. doi: 10.1016/j.febslet.2015.04.029. Epub 2015 Apr 29.

Abstract

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 p110α subunit of PI3K in Xenopus oocytes. In addition, inhibition of PI3K signaling by blocking p110α, 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.

Keywords: Akt; Connexin; Gap junction; Lens; PI3K.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Connexins / antagonists & inhibitors
  • Connexins / genetics
  • Connexins / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Gap Junctions / drug effects
  • Gap Junctions / metabolism*
  • Gene Silencing
  • HeLa Cells
  • Humans
  • Membrane Potentials / drug effects
  • Mutant Proteins / antagonists & inhibitors
  • Mutant Proteins / metabolism
  • Oocytes / drug effects
  • Oocytes / enzymology
  • Oocytes / metabolism*
  • Patch-Clamp Techniques
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation / drug effects
  • Protein Processing, Post-Translational / drug effects
  • RNA, Complementary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Second Messenger Systems* / drug effects
  • Single-Cell Analysis
  • Xenopus Proteins / antagonists & inhibitors
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis

Substances

  • Connexins
  • Enzyme Inhibitors
  • Mutant Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • RNA, Complementary
  • Recombinant Proteins
  • Xenopus Proteins
  • GJA3 protein, human
  • connexin 50
  • PIK3C2A protein, Xenopus