Essential roles for GSK-3s and GSK-3-primed substrates in neurotrophin-induced and hippocampal axon growth.

ABSTRACT: Glycogen synthase kinase-3beta (GSK-3beta) is thought to mediate morphological responses to a variety of extracellular signals. Surprisingly, we found no gross morphological deficits in nervous system development in GSK-3beta null mice. We therefore designed an shRNA that targeted both GSK-3 isoforms. Strong knockdown of both GSK-3alpha and beta markedly reduced axon growth in dissociated cultures and slice preparations. We then assessed the role of different GSK-3 substrates in regulating axon morphology. Elimination of activity toward primed substrates only using the GSK-3 R96A mutant was associated with a defect in axon polarity (axon branching) compared to an overall reduction in axon growth induced by a kinase-dead mutant. Consistent with this finding, moderate reduction of GSK-3 acti

SUBMITTER: Kim WY 

PROVIDER: S-EPMC4167845 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature