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 α, β1, and β2 subunits. The auxiliary β subunits do not form the ion conducting pore, yet play important roles in channel modulation and plasma membrane expression. β1 and β2 are transmembrane proteins with one extracellular V-set immunoglobulin (Ig) protein domain. It has been shown recently that β1 and β2 interact with the extracellular matrix proteins tenascin-C and tenascin-R. In the present study we show that rat brain β1 and β2, but not αIIA, 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 αIIA subunits expressed alone do not cause cellular aggregation, β subunits co-expressed with αIIA retain the ability to adhere and recruit ankyrin. Truncated β subunits lacking cytoplasmic domains interact homophilically to produce cell aggregation but do not recruit ankyrin. Thus, the cytoplasmic domains of β1 and β2 are required for cytoskeletal interactions. It is hypothesized that sodium channel β 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.