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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western / methods
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COS Cells
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Calcium Channels / physiology*
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Cell Membrane / metabolism*
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Cells, Cultured
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Electric Stimulation / methods
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Ganglia, Spinal / cytology
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Gene Expression Regulation / physiology*
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Green Fluorescent Proteins
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Haplorhini
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Immunohistochemistry
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Insulin-Like Growth Factor I / pharmacology
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Luminescent Proteins / metabolism
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Membrane Potentials / physiology
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Microscopy, Confocal / methods
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Molecular Sequence Data
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Mutation / physiology
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Neurons / cytology*
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Patch-Clamp Techniques / methods
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Phosphatidylinositol 3-Kinases / physiology*
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Phosphatidylinositols / metabolism
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Protein Serine-Threonine Kinases / metabolism
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Protein Subunits / genetics
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Protein Subunits / metabolism
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Protein Transport / physiology
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Rabbits
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Rats
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Serine / genetics
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Serine / metabolism
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Transfection / methods
Substances
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Calcium Channels
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Luminescent Proteins
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Phosphatidylinositols
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Protein Subunits
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Proto-Oncogene Proteins
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Green Fluorescent Proteins
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Serine
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Insulin-Like Growth Factor I
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Akt1 protein, rat
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
Associated data
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GENBANK/D14157
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GENBANK/L02315
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GENBANK/M61745
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GENBANK/M62653
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GENBANK/M67515
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GENBANK/M80545
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GENBANK/M86621
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GENBANK/M88751
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GENBANK/M93252
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GENBANK/X61394
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GENBANK/X83368
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GENBANK/Y10742