Open AccessNeuronal polarity is regulated by glycogen synthase kinase-3 (GSK-3β) independently of Akt/PKB serine phosphorylation
Author(s) -
Agnès Gartner,
Xu Huang,
Alan Hall
Publication year - 2006
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.03159
Subject(s) - gsk 3 , biology , phosphorylation , neurite , microbiology and biotechnology , protein kinase b , gsk3b , growth cone , axon , kinase , axoplasmic transport , cell polarity , biochemistry , cell , in vitro
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-3β (GSK-3β) 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We now report that, by using neurons from double knock-in mice in which Ser9 and Ser21 of the two GSK-3β isoforms have been replaced by Ala, polarity develops independently of phosphorylation at these sites. Nevertheless, global inhibition of GSK-3β 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-3β leads to APC protein accumulation in all neurites. We conclude that GSK-3β inhibition promotes the development of neuronal polarity, but that this is not mediated by Akt/PKB-dependent phosphorylation.