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

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