Anterograde Transport of TrkB in Axons Is Mediated by Direct Interaction with Slp1 and Rab27

Nariko Arimura, Toshihide Kimura, Shinichi Nakamuta, Shinichiro Taya, Yasuhiro Funahashi, Atsushi Hattori, Akiko Shimada, Céline Ménager, Saeko Kawabata, Kayo Fujii, Akihiro Iwamatsu, Rosalind A. Segal, Mitsunori Fukuda, Kozo Kaibuchi

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

The neurotrophin receptors TrkA, TrkB, and TrkC are localized at the surface of the axon terminus and transmit key signals from brain-derived neurotrophic factor (BDNF) for diverse effects on neuronal survival, differentiation, and axon formation. Trk receptors are sorted into axons via the anterograde transport of vesicles and are then inserted into axonal plasma membranes. However, the transport mechanism remains largely unknown. Here, we show that the Slp1/Rab27B/CRMP-2 complex directly links TrkB to Kinesin-1, and that this association is required for the anterograde transport of TrkB-containing vesicles. The cytoplasmic tail of TrkB binds to Slp1 in a Rab27B-dependent manner, and CRMP-2 connects Slp1 to Kinesin-1. Knockdown of these molecules by siRNA reduces the anterograde transport and membrane targeting of TrkB, thereby inhibiting BDNF-induced ERK1/2 phosphorylation in axons. Our data reveal a molecular mechanism for the selective anterograde transport of TrkB in axons and show how the transport is coupled to BDNF signaling.

Original languageEnglish
Pages (from-to)675-686
Number of pages12
JournalDevelopmental cell
Volume16
Issue number5
DOIs
Publication statusPublished - 2009 May 19

Keywords

  • CELLBIO
  • MOLNEURO

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Arimura, N., Kimura, T., Nakamuta, S., Taya, S., Funahashi, Y., Hattori, A., Shimada, A., Ménager, C., Kawabata, S., Fujii, K., Iwamatsu, A., Segal, R. A., Fukuda, M., & Kaibuchi, K. (2009). Anterograde Transport of TrkB in Axons Is Mediated by Direct Interaction with Slp1 and Rab27. Developmental cell, 16(5), 675-686. https://doi.org/10.1016/j.devcel.2009.03.005