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Miyamoto Y, Torii T, Kawahara K, et al. Dock8 interacts with Nck1 in mediating Schwann cell precursor migration. Biochem Biophys Rep. 2016;6:113-123doi: 10.1016/j.bbrep.2016.03.013.
Miyamoto, Y., Torii, T., Kawahara, K., Tanoue, A., & Yamauchi, J. (2016). Dock8 interacts with Nck1 in mediating Schwann cell precursor migration. Biochemistry and biophysics reports, 6113-123. https://doi.org/10.1016/j.bbrep.2016.03.013
Miyamoto, Yuki, et al. "Dock8 interacts with Nck1 in mediating Schwann cell precursor migration." Biochemistry and biophysics reports vol. 6 (2016): 113-123. doi: https://doi.org/10.1016/j.bbrep.2016.03.013
Miyamoto Y, Torii T, Kawahara K, Tanoue A, Yamauchi J. Dock8 interacts with Nck1 in mediating Schwann cell precursor migration. Biochem Biophys Rep. 2016 Mar 24;6:113-123. doi: 10.1016/j.bbrep.2016.03.013. eCollection 2016 Jul. PMID: 28955869; PMCID: PMC5600352.
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Biochem Biophys Rep. 2016 Mar 24;6:113-123. doi: 10.1016/j.bbrep.2016.03.013. eCollection 2016 Jul.

Dock8 interacts with Nck1 in mediating Schwann cell precursor migration.

Biochemistry and biophysics reports

Yuki Miyamoto, Tomohiro Torii, Kazuko Kawahara, Akito Tanoue, Junji Yamauchi

Affiliations

  1. Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
  2. Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo 113-8510, Japan.

PMID: 28955869 PMCID: PMC5600352 DOI: 10.1016/j.bbrep.2016.03.013

Abstract

During embryonic development of the peripheral nervous system (PNS), Schwann cell precursors migrate along neuronal axons to their final destinations, where they will myelinate the axons after birth. While the intercellular signals controlling Schwann cell precursor migration are well studied, the intracellular signals controlling Schwann cell precursor migration remain elusive. Here, using a rat primary cell culture system, we show that Dock8, an atypical Dock180-related guanine-nucleotide exchange factor (GEF) for small GTPases of the Rho family, specifically interacts with Nck1, an adaptor protein composed only of Src homology (SH) domains, to promote Schwann cell precursor migration induced by platelet-derived growth factor (PDGF). Knockdown of Dock8 or Nck1 with its respective siRNA markedly decreases PDGF-induced cell migration, as well as Rho GTPase activation, in precursors. Dock8, through its unique N-terminal proline-rich motif, interacts with the SH3 domain of Nck1, but not with other adaptor proteins composed only of SH domains, e.g. Grb2 and CrkII, and not with the adaptor protein Elmo1. Reintroduction of the proline-rich motif mutant of Dock8 in Dock8 siRNA-transfected Schwann cell precursors fails to restore their migratory abilities, whereas that of wild-type Dock8 does restore these abilities. These results suggest that Nck1 interaction with Dock8 mediates PDGF-induced Schwann cell precursor migration, demonstrating not only that Nck1 and Dock8 are previously unanticipated intracellular signaling molecules involved in the regulation of Schwann cell precursor migration but also that Dock8 is among the genetically-conservative common interaction subset of Dock family proteins consisting only of SH domain adaptor proteins.

Keywords: Dock8; Migration; Nck1; PDGF; Schwann cell precursor

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