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 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.
The Department of Physiology & Biophysics, Stony Brook University, Stony Brook, NY 11794-8661, USA.
Jennifer M
JM
Martinez
The Department of Physiology & Biophysics, Stony Brook University, Stony Brook, NY 11794-8661, USA.
Hong-Zhan
HZ
Wang
The Department of Physiology & Biophysics, Stony Brook University, Stony Brook, NY 11794-8661, USA.
Richard Z
RZ
Lin
The Department of Physiology & Biophysics, Stony Brook University, Stony Brook, NY 11794-8661, USA.
Peter R
PR
Brink
The Department of Physiology & Biophysics, Stony Brook University, Stony Brook, NY 11794-8661, USA. Electronic address: thomas.white@stonybrook.edu.
Thomas W
TW
White
D000818:Animals; D017630:Connexins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D050505:Mutant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D018075:RNA, Complementary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D059010:Single-Cell Analysis; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis; D000099264:Connexin 50
D017630:Connexins; D004791:Enzyme Inhibitors; D050505:Mutant Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018075:RNA, Complementary; D011994:Recombinant Proteins; D029867:Xenopus Proteins; D000099264:Connexin 50; C082917:GJA3 protein, human; C000599701:PIK3C2A protein, Xenopus
Akt; Connexin; Gap junction; Lens; PI3K