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Originally published In Press as doi:10.1074/jbc.M108699200 on October 1, 2001

J. Biol. Chem., Vol. 276, Issue 49, 46553-46561, December 7, 2001
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Direct Interaction with Contactin Targets Voltage-gated Sodium Channel Nav1.9/NaN to the Cell Membrane*

Chuan-ju LiuDagger §, Sulayman D. Dib-HajjDagger §, Joel A. BlackDagger §, John Greenwood||, Zheng Lian**, and Stephen G. WaxmanDagger §Dagger Dagger

From the Dagger  Department of Neurology and § Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Neuroscience Research Center, Yale University School of Medicine, New Haven, Connecticut 06510,  Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut 06516, || TransMolecular, Inc., Birmingham, Alabama 35243, and the ** Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06536

The mechanisms that target various sodium channels within different regions of the neuronal membrane, which they endow with different physiological properties, are not yet understood. To examine this issue we studied the voltage-gated sodium channel Nav1.9/NaN, which is preferentially expressed in small sensory neurons of dorsal root ganglia and trigeminal ganglia and the nonmyelinated axons that arise from them. Our results show that the cell adhesion molecule contactin binds directly to Nav1.9/NaN and recruits tenascin to the protein complex in vitro. Nav1.9/NaN and contactin co-immunoprecipitate from dorsal root ganglia and transfected Chinese hamster ovary cell line, and co-localize in the C-type neuron soma and along nonmyelinated C-fibers and at nerve endings in the skin. Co-transfection of Chinese hamster ovary cells with Nav1.9/NaN and contactin enhances the surface expression of the sodium channel over that of Nav1.9/NaN alone. Thus contactin binds directly to Nav1.9/NaN and participates in the surface localization of this channel along nonmyelinated axons.


* This work was supported in part by grants from the National Multiple Sclerosis Society and the Rehabilitation Research and Development Service and Medical Research Service, Department of Veterans Affairs, and by gifts from the Paralyzed Veterans of America and Eastern Paralyzed Veterans Association.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Dagger To whom correspondence should be addressed: Dept. of Neurology LCI 707, Yale Medical School, 333 Cedar St., New Haven, CT 06510. Tel.: 203-785-6351; Fax: 203-785-7826; E-mail: stephen.waxman@yale.edu.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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