title: 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 β-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 Cavβ subunit isoforms, affecting their subcellular localization and suppressing VGCC activity. Domain I interacts at the α1 interaction domain-binding pocket in Cavβ and interferes with the association between Cavβ and Cavα1. In the absence of domain I binding, BARP can form a ternary complex with Cavα1 and Cavβ via domain II. BARP does not affect cell surface expression of Cavα1 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 Cavβ and its association with the Cavα1 subunit to negatively regulate VGCC activity.
authors.affiliation: Epithelial Cell Biology Laboratory and 2 Monoclonal Antibody Unit, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.
authors.forename: Pascal
authors.initials: P
authors.lastname: Béguin
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nagashima
authors.forename: Ramasubbu N
authors.initials: RN
authors.lastname: Mahalakshmi
authors.forename: Réjan
authors.initials: R
authors.lastname: Vigot
authors.forename: Atsuko
authors.initials: A
authors.lastname: Matsunaga
authors.forename: Takafumi
authors.initials: T
authors.lastname: Miki
authors.forename: Mei Yong
authors.initials: MY
authors.lastname: Ng
authors.forename: Yu Jin Alvin
authors.initials: YJ
authors.lastname: Ng
authors.forename: Chiaw Hwee
authors.initials: CH
authors.lastname: Lim
authors.forename: Hock Soon
authors.initials: HS
authors.lastname: Tay
authors.forename: Le-Ann
authors.initials: LA
authors.lastname: Hwang
authors.forename: Dmitri
authors.initials: D
authors.lastname: Firsov
authors.forename: Bor Luen
authors.initials: BL
authors.lastname: Tang
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
authors.forename: Thomas
authors.initials: T
authors.lastname: Launey
authors.forename: Walter
authors.initials: W
authors.lastname: Hunziker
mesh_terms: D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006224:Cricetinae; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055099:Neuroendocrine Cells / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats
chemical_list: C000588793:BARP protein, mouse; C000588794:BARP protein, rat; C000588792:CBARP protein, human; D020746:Calcium Channels, L-Type; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D002118:Calcium
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