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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 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 Na_v1.2 and 1 subunits and contactin have threefold to fourfold higher peak Na⁺ currents than cells with Na_v1.2 alone, Na_v1.2/1, Na_v1.2/contactin, or Na_v1.2/1/2. 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 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; subunit; axon; cluster

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

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