PI3K promotes voltage-dependent calcium channel trafficking to the plasma membrane
P Viard, AJ Butcher, G Halet, A Davies… - Nature …, 2004 - nature.com
P Viard, AJ Butcher, G Halet, A Davies, B Nürnberg, F Heblich, AC Dolphin
Nature neuroscience, 2004•nature.comAbstract 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 Cavβ2 subunits. The mutations S574A and S574E in Cavβ2a prevented …
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 Cavβ2 subunits. The mutations S574A and S574E in Cavβ2a prevented …
Abstract
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 Cavβ2 subunits. The mutations S574A and S574E in Cavβ2a prevented and mimicked, respectively, the effect of PI3K/Akt-PKB, indicating that phosphorylation of Ser574 on Cavβ2a is necessary and sufficient to promote Cav channel trafficking.
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