Regulation of PI3K signalling by the phosphatidylinositol transfer protein PITPalpha 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 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.
Cosker
Katharina E
KE
MRC Centre for Developmental Neurobiology, King's College London, London, SE1 1UL, UK.
Shadan
Sadaf
S
van Diepen
Michiel
M
Morgan
Clive
C
Li
Michelle
M
Allen-Baume
Victoria
V
Hobbs
Carl
C
Doherty
Patrick
P
Cockcroft
Shamshad
S
Eickholt
Britta J
BJ
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
D049294:Phospholipid Transfer Proteins; D019869:Phosphatidylinositol 3-Kinases