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First published online 19 February 2008
doi: 10.1242/jcs.019166

Journal of Cell Science 121, 796-803 (2008)
Published by The Company of Biologists 2008
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Research Article

Regulation of PI3K signalling by the phosphatidylinositol transfer protein PITP{alpha} during axonal extension in hippocampal neurons

Katharina E. Cosker1, Sadaf Shadan2, Michiel van Diepen1, Clive Morgan2, Michelle Li2, Victoria Allen-Baume2, Carl Hobbs3, Patrick Doherty3, Shamshad Cockcroft2 and Britta J. Eickholt1,*

1 MRC Centre for Developmental Neurobiology, King's College London, London, SE1 1UL, UK
2 Department of Physiology, University College London, London, WC1E 6JJ, UK
3 Wolfson Centre for Age-Related Diseases, King's College London, London, SE1 1UL, UK

* Author for correspondence (e-mail: Britta.J.Eickholt{at}kcl.ac.uk)

Accepted 17 December 2007

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 PITPβ or a PITP{alpha} mutant deficient in binding PtdIns, enhances laminin-dependent extension of axonal processes in hippocampal neurons, whereas knockdown of PITP{alpha} 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.

Key words: PITP, Axonal elongation, Phosphoinositide 3-kinase, Hippocampal neurons






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