Differential interaction of voltage-gated K+ channel beta-subunits with cytoskeleton is mediated by unique amino terminal domains.

To define the molecular characteristics of K+ channel beta-subunit polypeptides, we have studied their biochemical properties and subcellular distribution in transfected mammalian cells. We find that the recombinant voltage-dependent K+ (Kv) beta1.1 and Kvbeta2 polypeptides have distinct detergent solubility properties owing to a novel association of Kvbeta1.1 with the actin-based cytoskeleton. Mutational and chimeric protein analyses show that the unique aminoterminus of Kvbeta1.1 is both necessary and sufficient for mediating the association of beta-subunits with cytoskeleton. Thus, the interaction with cytoskeleton is mediated through the amino-terminal domain previously shown to be necessary for modulating alpha-subunit inactivation, but not necessary for interaction with alpha-subunit polypeptides. These data reveal that different domains of beta-subunit polypeptides mediate interactions with cytoskeleton and with alpha-subunits, and provide a structural basis for previous reports that linked the extent of beta-subunit-induced inactivation to the state of the actin cytoskeleton.