title: Contactin associates with Na+ channels and increases their functional expression.
abstract: 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.
authors.affiliation: Departments of Neurobiology/Anatomy and Biochemistry/Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kazarinova-Noyes
authors.forename: J D
authors.initials: JD
authors.lastname: Malhotra
authors.forename: D P
authors.initials: DP
authors.lastname: McEwen
authors.forename: L N
authors.initials: LN
authors.lastname: Mattei
authors.forename: E O
authors.initials: EO
authors.lastname: Berglund
authors.forename: B
authors.initials: B
authors.lastname: Ranscht
authors.forename: S R
authors.initials: SR
authors.lastname: Levinson
authors.forename: M
authors.initials: M
authors.lastname: Schachner
authors.forename: P
authors.initials: P
authors.lastname: Shrager
authors.forename: L L
authors.initials: LL
authors.lastname: Isom
authors.forename: Z C
authors.initials: ZC
authors.lastname: Xiao
mesh_terms: 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
chemical_list: 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