PMID- 19460344 OWN - NLM STAT- MEDLINE DCOM- 20090615 LR - 20161125 IS - 1878-1551 (Electronic) IS - 1534-5807 (Linking) VI - 16 IP - 5 DP - 2009 May TI - Anterograde transport of TrkB in axons is mediated by direct interaction with Slp1 and Rab27. PG - 675-86 LID - 10.1016/j.devcel.2009.03.005 [doi] AB - 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. FAU - Arimura, Nariko AU - Arimura N AD - Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Showa, Nagoya, Japan. FAU - Kimura, Toshihide AU - Kimura T FAU - Nakamuta, Shinichi AU - Nakamuta S FAU - Taya, Shinichiro AU - Taya S FAU - Funahashi, Yasuhiro AU - Funahashi Y FAU - Hattori, Atsushi AU - Hattori A FAU - Shimada, Akiko AU - Shimada A FAU - Menager, Celine AU - Menager C FAU - Kawabata, Saeko AU - Kawabata S FAU - Fujii, Kayo AU - Fujii K FAU - Iwamatsu, Akihiro AU - Iwamatsu A FAU - Segal, Rosalind A AU - Segal RA FAU - Fukuda, Mitsunori AU - Fukuda M FAU - Kaibuchi, Kozo AU - Kaibuchi K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Dev Cell JT - Developmental cell JID - 101120028 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carrier Proteins) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 3.6.1.- (Rab27b protein, rat) RN - EC 3.6.5.2 (rab GTP-Binding Proteins) SB - IM MH - Animals MH - *Axonal Transport MH - Brain-Derived Neurotrophic Factor/metabolism MH - Carrier Proteins/*metabolism MH - Rats MH - Receptor, trkB/*metabolism MH - rab GTP-Binding Proteins/*metabolism EDAT- 2009/05/23 09:00 MHDA- 2009/06/16 09:00 CRDT- 2009/05/23 09:00 PHST- 2008/07/09 00:00 [received] PHST- 2008/11/25 00:00 [revised] PHST- 2009/03/03 00:00 [accepted] PHST- 2009/05/23 09:00 [entrez] PHST- 2009/05/23 09:00 [pubmed] PHST- 2009/06/16 09:00 [medline] AID - S1534-5807(09)00095-1 [pii] AID - 10.1016/j.devcel.2009.03.005 [doi] PST - ppublish SO - Dev Cell. 2009 May;16(5):675-86. doi: 10.1016/j.devcel.2009.03.005.