Neurotrophin 3 activation of TrkC induces Schwann cell migration through the c-Jun N-terminal kinase pathway

doi:10.1073/pnas.2336152100

Neurotrophin 3 activation of TrkC induces Schwann cell migration through the c-Jun N-terminal kinase pathway

^*Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305-5125; and ^†Department of Cell Biology, Nara Institute of Science and Technology, Nara 630-0101, Japan

Contributed by Eric M. Shooter, September 24, 2003

Abstract

During development and nerve injury, complex interactions between glial cells and neurons are essential for establishing proper nerve function. Neurotrophins play multiple roles in the developing nervous system, including cell survival, growth, and differentiation. Here we show that migration of Schwann cells, isolated from sciatic nerves, is significantly enhanced by neurotrophin 3, but not by nerve growth factor or brain-derived neurotrophic factor. The neurotrophin-3-induced cell migration was also observed in Schwann cells isolated from sciatic nerves of p75^NTR-/- mice, indicating that neurotrophin 3 enhances cell migration through TrkC. This effect was blocked by K252a, an inhibitor of the Trk receptor family. Additionally, the neurotrophin-3-induced cell migration depended on Rho GTPases (Rac1 and Cdc42) and c-Jun N-terminal kinase. We obtained the same results with Cos-7 cells expressing TrkC. Taken together, these results suggest that neurotrophin 3 activation of TrkC induces Schwann cell migration through the c-Jun N-terminal kinase signaling pathway.

Footnotes

↵ ‡ To whom correspondence should be addressed at: Department of Neurobiology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305-5125. E-mail: eshooter{at}cmgm.stanford.edu.
Abbreviations: BDNF, brain-derived neurotrophic factor; NT3, neurotrophin 3; NTR, neurotrophin receptor; GEF, guanine nucleotide-exchange factor; CRIB, Rac1·GTP- and Cdc42·GTP-binding domain; RBD, RhoA·GTP-binding domain; DRG, dorsal root ganglion; JNK, c-Jun N-terminal kinase; CA, constitutively active.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AY336094).