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

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.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

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

doi

10.1038/nn1300

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

939-46

issue

9

eissn

1097-6256

issn

1546-1726

pii

nn1300

journal_volume

7

pub_type

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