TY - JOUR
T1 - Anterograde Transport of TrkB in Axons Is Mediated by Direct Interaction with Slp1 and Rab27
AU - Arimura, Nariko
AU - Kimura, Toshihide
AU - Nakamuta, Shinichi
AU - Taya, Shinichiro
AU - Funahashi, Yasuhiro
AU - Hattori, Atsushi
AU - Shimada, Akiko
AU - Ménager, Céline
AU - Kawabata, Saeko
AU - Fujii, Kayo
AU - Iwamatsu, Akihiro
AU - Segal, Rosalind A.
AU - Fukuda, Mitsunori
AU - Kaibuchi, Kozo
N1 - Funding Information:
We thank R.Y. Tsien (UCSD); M. Igarashi (Niigata University); Y. Fukata (National Institute for Physiological Sciences); T. Suzuki (Hokkaido University); R.D. Burgoyne (University of Liverpool); M. Chao (New York University School of Medicine); and T. Watanabe, M. Takefuji, and N. Mishima (Nagoya University) for helpful discussions and preparation of some materials. We also thank T. Ishii for secretarial and technical assistance. This work was supported by Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency (JST); grant (S) 20227006 from grants-in-aid for scientific research (K.K.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); grant 15GS0319 from grants-in-aid for creative scientific research from the Japan Society for the Promotion of Science (JSPS) (K.K.); grant 17024024 from grants-in-aid for scientific research on priority areas from MEXT (K.K.); a grant-in-aid for GCOE research from MEXT; grant 20-9883 from grants-in-aid for JSPS Fellows (S.N.); grants (B) 18700314 and 20700332 (N.A.) from grants-in-aid for young scientists from MEXT; and research grant 18-8 for Nervous and Mental Disorders from the Ministry of Health, Labour and Welfare.
PY - 2009/5/19
Y1 - 2009/5/19
N2 - 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.
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.
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U2 - 10.1016/j.devcel.2009.03.005
DO - 10.1016/j.devcel.2009.03.005
M3 - Article
C2 - 19460344
AN - SCOPUS:65549104155
SN - 1534-5807
VL - 16
SP - 675
EP - 686
JO - Developmental Cell
JF - Developmental Cell
IS - 5
ER -