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

被引：204

作者：

Viard, P

Butcher, AJ

Halet, G

Davies, A

Nürnberg, B

Heblich, F

Dolphin, AC

机构：

[1] UCL, Dept Pharmacol, London WC1E 6BT, England

[2] UCL, Dept Physiol, London WC1E 6BT, England

[3] Univ Dusseldorf Klinikum, Inst Biochem & Mol Biol 2, D-40225 Dusseldorf, Germany

来源：

NATURE NEUROSCIENCE | 2004年 / 7卷 / 09期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

D O I：

10.1038/nn1300

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

收藏

页码：939 / 946

页数：8

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