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Neurotrophins regulate Schwann cell migration by activating divergent signaling pathways dependent on Rho GTPases.


ABSTRACT: Neurotrophins are recognized widely as essential factors in the developing nervous system. Previously, we demonstrated that neurotrophin 3 activation of TrkC inhibits Schwann cell myelination and enhances the migration of primary Schwann cells through the signaling pathway regulated by the Rho GTPases Rac1 and Cdc42. Here, we show that neurotrophins activate divergent signaling pathways to promote or inhibit Schwann cell migration. Endogenous brain-derived neurotrophic factor acting through p75(NTR) inhibits Schwann cell migration dramatically by Src kinase-dependent activation of the guanine-nucleotide exchange factor Vav2 and RhoA. Together, these results suggest that neurotrophins and their receptors differentially regulate Schwann cell migration through the signaling pathways that depend on Rho GTPases.

SUBMITTER: Yamauchi J 

PROVIDER: S-EPMC423271 | biostudies-literature | 2004 Jun

REPOSITORIES: biostudies-literature

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Neurotrophins regulate Schwann cell migration by activating divergent signaling pathways dependent on Rho GTPases.

Yamauchi Junji J   Chan Jonah R JR   Shooter Eric M EM  

Proceedings of the National Academy of Sciences of the United States of America 20040525 23


Neurotrophins are recognized widely as essential factors in the developing nervous system. Previously, we demonstrated that neurotrophin 3 activation of TrkC inhibits Schwann cell myelination and enhances the migration of primary Schwann cells through the signaling pathway regulated by the Rho GTPases Rac1 and Cdc42. Here, we show that neurotrophins activate divergent signaling pathways to promote or inhibit Schwann cell migration. Endogenous brain-derived neurotrophic factor acting through p75(  ...[more]

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