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Nature Research, Nature Neuroscience, 9(7), p. 939-946, 2004

DOI: 10.1038/nn1300

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

Journal article published in 2004 by Patricia Viard, Aj Butcher, Guillaume Halet, Anthony Davies, Bernd Nurnberg, Fay Heblich, Ac Dolphin ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.