citations

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

Authors:

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

In:

Source: Nat Neurosci
Publication Date: (2004)
Issue: 7(9): 939-946

Research Area:

Neurobiology

Cells used in publication:

Dorsal root gang. (DRG), rat: Species: rat; Tissue Origin: brain

Platform:

Nucleofector® I/II/2b

Experiment

Primary rat dorsal root ganglion neurons were transfected by nucleofection with plasmids expressing GFP-fusions of the pleckstrin homology domain of the general receptor for phosphoinositides (PHGrp1-GFP), which specifically binds phosphatidylinositol (3,4,5)-trisphosphate (PIP3), or of Ca(v) subunits Ca(v)2.2alpha1 and beta(2a).

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.

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