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

研究成果: ジャーナルへの寄稿学術論文査読

166 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)675-686
ページ数12
ジャーナルDevelopmental Cell
16
5
DOI
出版ステータス出版済み - 19-05-2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 生化学、遺伝学、分子生物学一般
  • 発生生物学
  • 細胞生物学

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