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The Journal of Neuroscience, October 1, 2001, 21(19):7517-7525

Contactin Associates with Na+ Channels and Increases Their Functional Expression

Katie Kazarinova-Noyes1, Jyoti Dhar Malhotra2, Dyke P. McEwen2, Laura N. Mattei2, Erik O. Berglund3, Barbara Ranscht3, S. Rock Levinson4, Melitta Schachner5, Peter Shrager1, Lori L. Isom2, and Zhi-Cheng Xiao1

1 Departments of Neurobiology/Anatomy and Biochemistry/Biophysics, University of Rochester Medical Center, Rochester, New York 14642, 2 Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109-0632, 3 Neuroscience Program, The Burnham Institute, La Jolla, California 92037, 4 Department of Physiology, University of Colorado Health Sciences Center, Denver, Colorado 80262, and 5 Zentrum fuer Molekulare Neurobiologie, Universitat Hamburg, D-20246 Hamburg, Germany

Contactin (also known as F3, F11) is a surface glycoprotein that has significant homology with the beta 2 subunit of voltage-gated Na+ channels. Contactin and Na+ channels can be reciprocally coimmunoprecipitated from brain homogenates, indicating association within a complex. Cells cotransfected with Na+ channel Nav1.2alpha and beta 1 subunits and contactin have threefold to fourfold higher peak Na+ currents than cells with Nav1.2alpha alone, Nav1.2/beta 1, Nav1.2/contactin, or Nav1.2/beta 1/beta 2. These cells also have a correspondingly higher saxitoxin binding, suggesting an increased Na+ channel surface membrane density. Coimmunoprecipitation of different subunits from cell lines shows that contactin interacts specifically with the beta 1 subunit. In the PNS, immunocytochemical studies show a transient colocalization of contactin and Na+ channels at new nodes of Ranvier forming during remyelination. In the CNS, there is a particularly high level of colocalization of Na+ channels and contactin at nodes both during development and in the adult. Contactin may thus significantly influence the functional expression and distribution of Na+ channels in neurons.

Key words: contactin; node of Ranvier; Na+ channel; beta subunit; axon; cluster


Copyright © 2001 Society for Neuroscience  0270-6474/01/21197517-09$05.00/0




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