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First published online 5 September 2006
doi: 10.1242/jcs.03159
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Research Article |
1 MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK
2 MRC Protein Phosphorylation Unit, MSI/WTB Complex, Dow Street, University of Dundee, Dundee, DD1 5EH, UK
* Author for correspondence (e-mail: a.gaertner{at}ucl.ac.uk)
Accepted 5 July 2006
An essential step during the development of hippocampal neurons is the polarised outgrowth of a single axon. Recently, it has been suggested that inhibition of glycogen synthase kinase-3ß (GSK-3ß) via Akt/PKB-dependent phosphorylation of Ser9, specifically at the tip of the presumptive axon, is required for selective axonal outgrowth. We now report that, by using neurons from double knock-in mice in which Ser9 and Ser21 of the two GSK-3ß isoforms have been replaced by Ala, polarity develops independently of phosphorylation at these sites. Nevertheless, global inhibition of GSK-3ß disturbs polarity development by leading to the formation of multiple axon-like processes in both control and knock-in neurons. This unpolarised outgrowth is accompanied by the symmetric delivery of membrane components to all neurites. Finally, the adenomatous polyposis coli (APC) protein accumulates at the tip of one neurite before and during axon elongation, but global inhibition of GSK-3ß leads to APC protein accumulation in all neurites. We conclude that GSK-3ß inhibition promotes the development of neuronal polarity, but that this is not mediated by Akt/PKB-dependent phosphorylation.
Key words: GSK-3, Neuronal polarity, Phosphorylation, APC, Axon
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