Acidic motif responsible for plasma membrane association of the voltage-dependent calcium channel β1b subunit

Voltage-dependent calcium channels consist of a pore-forming transmembrane alpha 1-subunit, which is known to associate with a number of accessory subunits, including alpha 2-delta- and beta-subunits. The beta-subunits, of which four have been identified (beta 1-4), are intracellular proteins that have marked effects on calcium channel trafficking and function. In a previous study, we observed that the beta 1b-subunit showed selective plasma membrane association when expressed alone in COS7 cells, whereas beta 3 and beta 4 did not. In this study, we have examined the basis for this, and have identified, by making chimeric beta-subunits, that the C-terminal region, which shows most diversity between beta-subunits, of beta 1b is responsible for its plasma membrane association. Furthermore we have identified, by deletion mutations, an 11-amino acid motif present in the C terminus of beta 1b but not in beta 3 (amino acids 547-556 of beta 1b, WEEEEDYEEE), which when deleted, reduces membrane association of beta 1b. Future research aims to identify what is binding to this sequence in beta 1b to promote membrane association of this calcium channel subunit. It is possible that such membrane association is important for the selective localization or clustering of particular calcium channels with which beta 1b is associated.