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 Nav1.2
and
1 subunits and contactin have threefold to fourfold higher peak
Na+ currents than cells with Nav1.2
alone, Nav1.2/
1, Nav1.2/contactin, or
Nav1.2/
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
Copyright © 2001 Society for Neuroscience 0270-6474/01/21197517-09$05.00/0