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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
Direct Interaction with Contactin Targets
Voltage-gated Sodium Channel Nav1.9/NaN to the Cell
Membrane*
Chuan-ju
Liu §¶,
Sulayman D.
Dib-Hajj §¶,
Joel A.
Black §¶,
John
Greenwood ,
Zheng
Lian**, and
Stephen G.
Waxman §¶
From the 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.

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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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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