Anterograde transport of TrkB in axons is mediated by direct interaction with Slp1 and Rab27.
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.
Arimura
Nariko
N
Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Showa, Nagoya, Japan.
Kimura
Toshihide
T
Nakamuta
Shinichi
S
Taya
Shinichiro
S
Funahashi
Yasuhiro
Y
Hattori
Atsushi
A
Shimada
Akiko
A
Ménager
Céline
C
Kawabata
Saeko
S
Fujii
Kayo
K
Iwamatsu
Akihiro
A
Segal
Rosalind A
RA
Fukuda
Mitsunori
M
Kaibuchi
Kozo
K
D000818:Animals; D001370:Axonal Transport; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D051381:Rats; D020813:Receptor, trkB / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D020813:Receptor, trkB; C512956:Rab27b protein, rat; D020691:rab GTP-Binding Proteins