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)1.2 alpha and beta1 subunits and contactin have threefold to fourfold higher peak Na+ currents than cells with Na(v)1.2 alpha 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.