Direct interaction with contactin targets voltage-gated sodium channel Na(v)1.9/NaN to the cell membrane.
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 Na(v)1.9/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 Na(v)1.9/NaN and recruits tenascin to the protein complex in vitro. Na(v)1.9/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 Na(v)1.9/NaN and contactin enhances the surface expression of the sodium channel over that of Na(v)1.9/NaN alone. Thus contactin binds directly to Na(v)1.9/NaN and participates in the surface localization of this channel along nonmyelinated axons.
Liu
C J
CJ
Department of Neurology and Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Neuroscience Research Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Dib-Hajj
S D
SD
Black
J A
JA
Greenwood
J
J
Lian
Z
Z
Waxman
S G
SG
D000818:Animals; D016466:CHO Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D058966:Contactins; D006224:Cricetinae; D007150:Immunohistochemistry; D015640:Ion Channel Gating; D008297:Male; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*; D019063:Tenascin / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; C113705:Scn11a protein, rat; D015222:Sodium Channels; D019063:Tenascin; C074638:tenascin R