Literature DB >> 15311280

PI3K promotes voltage-dependent calcium channel trafficking to the plasma membrane.

Patricia Viard1, Adrian J Butcher, Guillaume Halet, Anthony Davies, Bernd Nürnberg, Fay Heblich, Annette C Dolphin.   

Abstract

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.

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Year:  2004        PMID: 15311280     DOI: 10.1038/nn1300

Source DB:  PubMed          Journal:  Nat Neurosci        ISSN: 1097-6256            Impact factor:   24.884


  97 in total

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