R-Ras controls axon specification upstream of glycogen synthase kinase-3beta through integrin-linked kinase.
J Biol Chem
; 282(1): 303-18, 2007 Jan 05.
Article
em En
| MEDLINE
| ID: mdl-17107957
ABSTRACT
The initial event in establishing a polarized neuron is the specification of a single axon. Spatially regulated glycogen synthase kinase-3beta (GSK-3beta) activity is critical for specifying axon-dendrite fate; however, the upstream signaling of GSK-3beta in the determination of neuronal polarity still remains obscure. Here, we found that, in cultured hippocampal neurons, the small GTPase R-Ras selectively localized in a single neurite of stage 2 neurons and that its activity increased after plating and peaked between stages 2 and 3. Ectopic expression of R-Ras induced global inactivation of GSK-3beta and formation of multiple axons, whereas knockdown of endogenous R-Ras by RNA interference blocked GSK-3beta inactivation and axon formation. GSK-3beta inactivation and axon formation by R-Ras required integrin-linked kinase (ILK), and subcellular localization of ILK was strictly regulated by R-Ras-mediated phosphatidylinositol 3-kinase activity. In addition, membrane targeting of ILK was sufficient to inactivate GSK-3beta and to form multiple axons. Our study demonstrates a novel role of R-Ras and ILK upstream of GSK-3beta in the regulation of neuronal polarity.
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Base de dados:
MEDLINE
Assunto principal:
Axônios
/
Proteínas Serina-Treonina Quinases
/
Proteínas ras
/
Quinase 3 da Glicogênio Sintase
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Japão