spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 19 Feb 2008
doi: 10.1242/jcs.019166

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.019166v1
121/6/796    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cosker, K. E.
Right arrow Articles by Eickholt, B. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cosker, K. E.
Right arrow Articles by Eickholt, B. J.

Research Article

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


Katharina E. Cosker, Sadaf Shadan, Michiel van Diepen, Clive Morgan, Michelle Li, Victoria Allen-Baume, Carl Hobbs, Patrick Doherty, Shamshad Cockcroft, and Britta J. Eickholt*
* Author for correspondence (e-mail: Britta.J.Eickholt{at}kcl.ac.uk)

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 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.






© The Company of Biologists Ltd 2008