PI3K promotes voltage-dependent calcium channel trafficking to the plasma membrane.
Phosphatidylinositol 3-kinase (PI3K) has been shown to enhance native voltage-dependent calcium channel (Ca(v)) currents both in myocytes and in neurons; however, the mechanism(s) responsible for this regulation were not known. Here we show that PI3K promotes the translocation of GFP-tagged Ca(v) channels to the plasma membrane in both COS-7 cells and neurons. We show that the effect of PI3K is mediated by Akt/PKB and specifically requires Ca(v)beta(2) subunits. The mutations S574A and S574E in Ca(v)beta(2a) prevented and mimicked, respectively, the effect of PI3K/Akt-PKB, indicating that phosphorylation of Ser574 on Ca(v)beta(2a) is necessary and sufficient to promote Ca(v) channel trafficking.
Department of Pharmacology, University College London, London WC1E 6BT, UK. p.viard@ucl.ac.uk
Patricia
P
Viard
Adrian J
AJ
Butcher
Guillaume
G
Halet
Anthony
A
Davies
Bernd
B
Nürnberg
Fay
F
Heblich
Annette C
AC
Dolphin
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D019556:COS Cells; D015220:Calcium Channels / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D004558:Electric Stimulation / Q000379:methods; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000502:physiology*; D049452:Green Fluorescent Proteins; D000882:Haplorhini; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008164:Luminescent Proteins / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D018613:Microscopy, Confocal / Q000379:methods; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D009474:Neurons / Q000166:cytology*; D018408:Patch-Clamp Techniques / Q000379:methods; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011817:Rabbits; D051381:Rats; D012694:Serine / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods
D015220:Calcium Channels; D049452:Green Fluorescent Proteins; D007334:Insulin-Like Growth Factor I; D008164:Luminescent Proteins; D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols; D017346:Protein Serine-Threonine Kinases; D021122:Protein Subunits; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine; C494920:Akt1 protein, rat