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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Brain-Derived Neurotrophic Factor / pharmacology
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Cell Movement / drug effects
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Cell Movement / physiology*
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Cells, Cultured
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Enzyme Activation / drug effects
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Mice
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Nerve Growth Factors / physiology*
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Neurotrophin 3 / pharmacology
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Neurotrophin 3 / physiology
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Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-vav
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Rats
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Receptor, Nerve Growth Factor
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Receptor, trkB / physiology
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Receptor, trkC / physiology
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Receptors, Nerve Growth Factor / physiology
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Schwann Cells / drug effects
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Schwann Cells / physiology*
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Signal Transduction
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rho GTP-Binding Proteins / physiology*
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rhoA GTP-Binding Protein / physiology
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src-Family Kinases / physiology
Substances
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Brain-Derived Neurotrophic Factor
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Nerve Growth Factors
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Neurotrophin 3
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Oncogene Proteins
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Proto-Oncogene Proteins c-vav
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Receptor, Nerve Growth Factor
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Receptors, Nerve Growth Factor
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Vav2 protein, mouse
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Vav2 protein, rat
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Receptor, trkB
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Receptor, trkC
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src-Family Kinases
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rho GTP-Binding Proteins
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rhoA GTP-Binding Protein