Ras activation of a Rac1 exchange factor, Tiam1, mediates neurotrophin-3-induced Schwann cell migration

Endogenous neurotrophins positively and negatively regulate migration of premyelinating Schwann cells before the initiation of myelination. Neurotrophin-3 (NT3) acting through the TrkC receptor tyrosine kinase stimulates Schwann cell migration via the Rho GTPases Rac1 and Cdc42. We previously demons...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2005-10, Vol.102 (41), p.14889-14894
Main Authors: Yamauchi, Junji, Miyamoto, Yuki, Tanoue, Akito, Shooter, Eric M, Chan, Jonah R
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Biological Sciences
cdc42 GTP-Binding Protein - metabolism
Cell division
Cell Movement - physiology
Fluorescent Antibody Technique
Guanine Nucleotide Exchange Factors - metabolism
Immunoblotting
Immunoprecipitation
Lymphoma
Neoplasm Proteins - metabolism
Neurotrophin 3 - metabolism
ras Proteins - metabolism
Rats
Rats, Sprague-Dawley
RNA, Small Interfering - genetics
Schwann Cells - metabolism
Schwann Cells - physiology
T-Lymphoma Invasion and Metastasis-inducing Protein 1
Transfection
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Summary:Endogenous neurotrophins positively and negatively regulate migration of premyelinating Schwann cells before the initiation of myelination. Neurotrophin-3 (NT3) acting through the TrkC receptor tyrosine kinase stimulates Schwann cell migration via the Rho GTPases Rac1 and Cdc42. We previously demonstrated that TrkC directly phosphorylates and activates Dbs, the guanine-nucleotide exchange factor (GEF) for Cdc42, to partially mediate Schwann cell migration. Here, we identify T lymphoma invasion and metastasis (Tiam) 1 as the Rac1-specific guanine-nucleotide exchange factor involved in NT3-induced Schwann cell migration. Furthermore, the interaction between the small GTPase Ras and Tiam1 plays an essential role in the activation of Rac1. Taken together, these results suggest that NT3 activation of TrkC stimulates Schwann cell migration through two parallel signaling units, Ras/Tiam1/Rac1 and Dbs/Cdc42, and that Schwann cell migration is uniquely regulated in the case of Ras and Rac1, by two different types of small GTPases. small GTPase TrkC
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0507125102