Sodium channel beta 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 cond ucting pore, yet play important roles in channel modulation and plasma memb rane expression, beta 1 and beta 2 are transmembrane proteins with one extr acellular V-set immunoglobulin (Ig) protein domain. It has been shown recen tly 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 f ashion, resulting in recruitment of the cytoskeletal protein ankyrin to sit es of cell-cell contact in transfected Drosophila S2 cells. Whereas alpha I IA subunits expressed alone do not cause cellular aggregation, beta subunit s co-expressed with alpha IIA retain the ability to adhere and recruit anky rin, Truncated beta subunits lacking cytoplasmic domains interact homophili cally to produce cell aggregation but do not recruit ankyrin, Thus, the cyt oplasmic domains of beta 1 and beta 2 are required for cytoskeletal interac tions. It is hypothesized that sodium channel beta subunits serve as a crit ical communication link between the extracellular and intracellular environ ments of the neuron and may play a role in sodium channel placement at node s of Ranvier.