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The Journal of Neuroscience, 2001, 21:RC125:1-7

RAPID COMMUNICATION
Association of Trk Neurotrophin Receptors with Components of the Cytoplasmic Dynein Motor

Hiroko Yano¹, Francis S. Lee², Haeyoung Kong¹, Jen-Zen Chuang³, Juan Carlos Arevalo¹, Pilar Perez⁴, Ching-Hwa Sung³, and Moses V. Chao¹

¹ Molecular Neurobiology Program, Skirball Institute for Biomolecular Medicine, Departments of Cell Biology and Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, ² Department of Psychiatry and ³ Departments of Cell Biology and Anatomy and Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Medical College of Cornell University, New York, New York 10021, and ⁴ Instituto de Microbiologia Bioquimica, Consejo Superior de Investigaciones Científicas/Universidad de Salamanca, 37007 Salamanca, Spain

Nerve growth factor (NGF) initiates its trophic effects by long-range signaling through binding, internalization, and transport of a ligand-receptor complex from the axon terminal to the cell body. However, the mechanism by which retrograde transport of NGF takes place has not been elucidated. Here we describe an interaction between the Trk receptor tyrosine kinase and a 14 kDa light chain of cytoplasmic dynein. After transfection in human embryonic kidney 293 cells, this 14 kDa dynein light chain was found to bind to TrkA, TrkB, and TrkC receptors. Mapping experiments indicated that the 14 kDa dynein light chain binds to the distal region of the TrkA juxtamembrane domain. Coimmunoprecipitation experiments in vivo indicate that Trk receptors are in a complex with the 14 kDa light chain and 74 kDa intermediate chain 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 receptors with components of cytoplasmic dynein suggests that transport of neurotrophins during vesicular trafficking may occur through a direct interaction of the Trk receptor with the dynein motor machinery.

Key words: NGF; Trk receptor; cytoplasmic dynein; retrograde transport; sciatic nerve; ligation

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Copyright © Society for Neuroscience  0270-6474//$05.00/0

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