RGD Reference Report - BARP suppresses voltage-gated calcium channel activity and Ca2+-evoked exocytosis. - Rat Genome Database

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

Authors: Beguin, P  Nagashima, K  Mahalakshmi, RN  Vigot, R  Matsunaga, A  Miki, T  Ng, MY  Ng, YJ  Lim, CH  Tay, HS  Hwang, LA  Firsov, D  Tang, BL  Inagaki, N  Mori, Y  Seino, S  Launey, T  Hunziker, W 
Citation: Beguin P, etal., J Cell Biol. 2014 Apr 28;205(2):233-49. doi: 10.1083/jcb.201304101. Epub 2014 Apr 21.
RGD ID: 10047103
Pubmed: (View Article at PubMed) PMID:24751537
DOI: Full-text: DOI:10.1083/jcb.201304101

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 beta-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 Cavbeta subunit isoforms, affecting their subcellular localization and suppressing VGCC activity. Domain I interacts at the alpha1 interaction domain-binding pocket in Cavbeta and interferes with the association between Cavbeta and Cavalpha1. In the absence of domain I binding, BARP can form a ternary complex with Cavalpha1 and Cavbeta via domain II. BARP does not affect cell surface expression of Cavalpha1 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 Cavbeta and its association with the Cavalpha1 subunit to negatively regulate VGCC activity.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Cacnb1  (calcium voltage-gated channel auxiliary subunit beta 1)
Cacnb2  (calcium voltage-gated channel auxiliary subunit beta 2)
Cacnb3  (calcium voltage-gated channel auxiliary subunit beta 3)
Cbarp  (CACN subunit beta associated regulatory protein)


Additional Information