Nature Neuroscience7, 939 - 946 (2004)
Published online: 15 August 2004; | doi:10.1038/nn1300
PI3K promotes voltage-dependent calcium channel trafficking to the plasma membrane
Patricia Viard1, Adrian J Butcher1, 4, Guillaume Halet2, 4, Anthony Davies1, Bernd Nürnberg3, Fay Heblich1
& Annette C Dolphin1
1
Department of Pharmacology, University College London, London WC1E 6BT, UK.
2
Department of Physiology, University College London, London WC1E 6BT, UK.
3
Institut für Biochemie und Molekular Biologie II, Klinikum der Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany.
4
These authors contributed equally to this work.
Correspondence should be addressed to Patricia Viard p.viard@ucl.ac.uk
Phosphatidylinositol 3-kinase (PI3K) has been shown to enhance native voltage-dependent calcium channel (Cav) 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 Cav 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 Cav2 subunits. The mutations S574A and S574E in Cav2a prevented and mimicked, respectively, the effect of PI3K/Akt-PKB, indicating that phosphorylation of Ser574 on Cav2a is necessary and sufficient to promote Cav channel trafficking.
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