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

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 PITP alpha is enriched in specific areas of the postnatal and adult brain, including the hippocampus and cerebellum. Overexpression of PITP alpha, but not PITP beta or a PITP alpha mutant deficient in binding PtdIns, enhances laminin-dependent extension of axonal processes in hippocampal neurons, whereas knockdown of PITPa protein by siRNA suppresses laminin and BDNF-induced axonal growth. PITP alpha-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 PITP alpha controls the polarized extension of axonal processes through the provision of PtdIns for localized PI3K-dependent signalling.