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    Nat Neurosci. 2004 Sep;7(9):939-46. Epub 2004 Aug 15.

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

    Viard P, Butcher AJ, Halet G, Davies A, Nürnberg B, Heblich F, Dolphin AC.

    Source

    Department of Pharmacology, University College London, London WC1E 6BT, UK. p.viard@ucl.ac.uk

    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.

    PMID:
    15311280
    [PubMed - indexed for MEDLINE]

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