Journal
JOURNAL OF CELL SCIENCE
Volume 121, Issue 6, Pages 796-803Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.019166
Keywords
PITP; axonal elongation; phosphoinositide 3-kinase; hippocampal neurons
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Funding
- MRC [G9900989] Funding Source: UKRI
- Medical Research Council [G9900989] Funding Source: researchfish
- Medical Research Council [G9900989] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
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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.
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