Sodium channel β subunits mediate homophilic cell adhesion and recruit ankyrin to points of cell-cell contact

Sodium channels isolated from mammalian brain are composed of alpha, beta 1, and beta 2 subunits, The auxiliary beta subunits do not form the ion conducting pore, yet play important roles in channel modulation and plasma membrane expression, beta 1 and beta 2 are transmembrane proteins with one extracellular V-set immunoglobulin (Ig) protein domain. It has been shown recently that beta 1 and beta 2 interact with the extracellular matrix proteins tenascin-C and tenascin-R, In the present study we show that rat brain beta 1 and beta 2, but not alpha IIA, subunits interact in a trans-homophilic fashion, resulting in recruitment of the cytoskeletal protein ankyrin to sites of cell-cell contact in transfected Drosophila S2 cells. Whereas alpha IIA subunits expressed alone do not cause cellular aggregation, beta subunits co-expressed with alpha IIA retain the ability to adhere and recruit ankyrin, Truncated beta subunits lacking cytoplasmic domains interact homophilically to produce cell aggregation but do not recruit ankyrin, Thus, the cytoplasmic domains of beta 1 and beta 2 are required for cytoskeletal interactions. It is hypothesized that sodium channel beta subunits serve as a critical communication link between the extracellular and intracellular environments of the neuron and may play a role in sodium channel placement at nodes of Ranvier.