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

Nat Neurosci. 2004 Sep;7(9):939-46. doi: 10.1038/nn1300. Epub 2004 Aug 15.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western / methods
  • COS Cells
  • Calcium Channels / physiology*
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Electric Stimulation / methods
  • Ganglia, Spinal / cytology
  • Gene Expression Regulation / physiology*
  • Green Fluorescent Proteins
  • Haplorhini
  • Immunohistochemistry
  • Insulin-Like Growth Factor I / pharmacology
  • Luminescent Proteins / metabolism
  • Membrane Potentials / physiology
  • Microscopy, Confocal / methods
  • Molecular Sequence Data
  • Mutation / physiology
  • Neurons / cytology*
  • Patch-Clamp Techniques / methods
  • Phosphatidylinositol 3-Kinases / physiology*
  • Phosphatidylinositols / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Protein Transport / physiology
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Rabbits
  • Rats
  • Serine / genetics
  • Serine / metabolism
  • Transfection / methods

Substances

  • Calcium Channels
  • Luminescent Proteins
  • Phosphatidylinositols
  • Protein Subunits
  • Proto-Oncogene Proteins
  • Green Fluorescent Proteins
  • Serine
  • Insulin-Like Growth Factor I
  • Akt1 protein, rat
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt

Associated data

  • GENBANK/D14157
  • GENBANK/L02315
  • GENBANK/M61745
  • GENBANK/M62653
  • GENBANK/M67515
  • GENBANK/M80545
  • GENBANK/M86621
  • GENBANK/M88751
  • GENBANK/M93252
  • GENBANK/X61394
  • GENBANK/X83368
  • GENBANK/Y10742