Acidic motif responsible for plasma membrane association of the voltage-dependent calcium channel beta 1b subunit

Voltage-dependent calcium channels consist of a pore-forming transmembrane alpha 1-subunit, which is known to associate with a number of accessory sub units, including alpha 2-delta- and beta-subunits. The beta-subunits, of wh ich four have been identified (beta 1-4), are intracellular proteins that h ave marked effects on calcium channel trafficking and function. In a previo us study, we observed that the beta 1b-subunit showed selective plasma memb rane association when expressed alone in COS7 cells, whereas beta 3 and bet a 4 did not. In this study, we have examined the basis for this, and have i dentified, by making chimeric beta-subunits, that the C-terminal region, wh ich shows most diversity between beta-subunits, of beta 1b is responsible f or its plasma membrane association. Furthermore we have identified, by dele tion 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 as sociation of this calcium channel subunit. It is possible that such membran e association is important for the selective localization or clustering of particular calcium channels with which beta 1b is associated.