title: Regulation of PI3K signalling by the phosphatidylinositol transfer protein PITPalpha during axonal extension in hippocampal neurons.
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.
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, London, SE1 1UL, UK.
authors.forename: Katharina E
authors.initials: KE
authors.lastname: Cosker
authors.forename: Sadaf
authors.initials: S
authors.lastname: Shadan
authors.forename: Michiel
authors.initials: M
authors.lastname: van Diepen
authors.forename: Clive
authors.initials: C
authors.lastname: Morgan
authors.forename: Michelle
authors.initials: M
authors.lastname: Li
authors.forename: Victoria
authors.initials: V
authors.lastname: Allen-Baume
authors.forename: Carl
authors.initials: C
authors.lastname: Hobbs
authors.forename: Patrick
authors.initials: P
authors.lastname: Doherty
authors.forename: Shamshad
authors.initials: S
authors.lastname: Cockcroft
authors.forename: Britta J
authors.initials: BJ
authors.lastname: Eickholt
mesh_terms: D000818:Animals; D001369:Axons / Q000201:enzymology / Q000648:ultrastructure*; D001921:Brain / Q000254:growth & development; D001923:Brain Chemistry; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction
chemical_list: D049294:Phospholipid Transfer Proteins; D019869:Phosphatidylinositol 3-Kinases