BARP suppresses voltage-gated calcium channel activity and Ca2+-evoked exocytosis.

ABSTRACT: Voltage-gated calcium channels (VGCCs) are key regulators of cell signaling and Ca(2+)-dependent release of neurotransmitters and hormones. Understanding the mechanisms that inactivate VGCCs to prevent intracellular Ca(2+) overload and govern their specific subcellular localization is of critical importance. We report the identification and functional characterization of VGCC ?-anchoring and -regulatory protein (BARP), a previously uncharacterized integral membrane glycoprotein expressed in neuroendocrine cells and neurons. BARP interacts via two cytosolic domains (I and II) with all Cav? subunit isoforms, affecting their subcellular localization and suppressing VGCC activity. Domain I interacts at the ?1 interaction domain-binding pocket in Cav? and interferes with the association between Cav? and Cav?1. In the absence of domain I binding, BARP can form a ternary complex with Cav?1 and Cav? via domain II. BARP does not affect cell surface expression of Cav?1 but inhibits Ca(2+) channel activity at the plasma membrane, resulting in the inhibition of Ca(2+)-evoked exocytosis. Thus, BARP can modulate the localization of Cav? and its association with the Cav?1 subunit to negatively regulate VGCC activity.

SUBMITTER: Beguin P 

PROVIDER: S-EPMC4003244 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature