Regulation of PI3K signalling by the phosphatidylinositol transfer protein PITPalpha during axonal extension in hippocampal neurons

J Cell Sci. 2008 Mar 15;121(Pt 6):796-803. doi: 10.1242/jcs.019166. Epub 2008 Feb 19.

Abstract

Phosphatidylinositol transfer proteins (PITPs) mediate the transfer of phosphatidylinositol (PtdIns) or phosphatidylcholine (PtdCho) between two membrane compartments, thereby regulating the interface between signalling, phosphoinositide (PI) metabolism and membrane traffic. Here, we show that PITPalpha is enriched in specific areas of the postnatal and adult brain, including the hippocampus and cerebellum. Overexpression of PITPalpha, but not PITPbeta or a PITPalpha mutant deficient in binding PtdIns, enhances laminin-dependent extension of axonal processes in hippocampal neurons, whereas knockdown of PITPalpha protein by siRNA suppresses laminin and BDNF-induced axonal growth. PITPalpha-mediated axonal outgrowth is sensitive to phosphoinositide 3-kinase (PI3K) inhibition and shows dependency on the Akt/GSK-3/CRMP-2 pathway. We conclude that PITPalpha controls the polarized extension of axonal processes through the provision of PtdIns for localized PI3K-dependent signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / enzymology
  • Axons / ultrastructure*
  • Brain / growth & development
  • Brain Chemistry
  • Cells, Cultured
  • Hippocampus / cytology
  • Hippocampus / embryology*
  • Hippocampus / growth & development
  • Neurons / chemistry
  • Neurons / cytology*
  • Neurons / enzymology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phospholipid Transfer Proteins / analysis
  • Phospholipid Transfer Proteins / antagonists & inhibitors
  • Phospholipid Transfer Proteins / metabolism*
  • RNA Interference
  • Rats
  • Signal Transduction

Substances

  • Phospholipid Transfer Proteins
  • Phosphatidylinositol 3-Kinases