Association of Trk neurotrophin receptors with components of the cytoplasmic dynein motor

Nerve growth factor (NGF) initiates its trophic effects by long-range signa ling through binding, internalization, and transport of a ligand-receptor c omplex from the axon terminal to the cell body. However, the mechanism by w hich retrograde transport of NGF takes place has not been elucidated. Here we describe an interaction between the Trk receptor tyrosine kinase and a 1 4 kDa light chain of cytoplasmic dynein. After transfection in human embryo nic kidney 293 cells, this 14 kDa dynein light chain was found to bind to T rkA, TrkB, and TrkC receptors. Mapping experiments indicated that the 14 kD a dynein light chain binds to the distal region of the TrkA juxtamembrane d omain. Coimmunoprecipitation experiments in vivo indicate that Trk receptor s are in a complex with the 14 kDa light chain and 74 kDa intermediate chai n of dynein. Confirming the physiological relevance of this association, a marked accumulation of Trk with the 14 kDa and the 74 kDa dynein components was observed after ligation of the sciatic nerve. The association of Trk r eceptors with components of cytoplasmic dynein suggests that transport of n eurotrophins during vesicular trafficking may occur through a direct intera ction of the Trk receptor with the dynein motor machinery.