Contactin associates with Na+ channels and increases their functional expression.
Contactin (also known as F3, F11) is a surface glycoprotein that has significant homology with the beta2 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(v)1.2alpha and beta1 subunits and contactin have threefold to fourfold higher peak Na(+) currents than cells with Na(v)1.2alpha alone, Na(v)1.2/beta1, Na(v)1.2/contactin, or Na(v)1.2/beta1/beta2. 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 beta1 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.
Kazarinova-Noyes
K
K
Departments of Neurobiology/Anatomy and Biochemistry/Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA.
Malhotra
J D
JD
McEwen
D P
DP
Mattei
L N
LN
Berglund
E O
EO
Ranscht
B
B
Levinson
S R
SR
Schachner
M
M
Shrager
P
P
Isom
L L
LL
Xiao
Z C
ZC
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry; D016466:CHO Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D058966:Contactins; D006224:Cricetinae; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology; D005260:Female; D015870:Gene Expression; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011233:Precipitin Tests; D021122:Protein Subunits; D011901:Ranvier's Nodes / Q000378:metabolism; D051381:Rats; D012530:Saxitoxin / Q000378:metabolism / Q000493:pharmacokinetics; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014162:Transfection
D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D008244:Lysophosphatidylcholines; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; C568253:Scn2A protein, rat; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012530:Saxitoxin; D013779:Tetrodotoxin; D012964:Sodium