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

Béguin, Pascal; Nagashima, Kazuaki; Mahalakshmi, Ramasubbu N.; Vigot, Réjan; Matsunaga, Atsuko; Miki, Takafumi; Ng, Mei Yong; Ng, Yu Jin Alvin; Lim, Chiaw Hwee; Tay, Hock Soon; Hwang, Le-Ann; Firsov, Dmitri; Tang, Bor Luen; Inagaki, Nobuya; Mori, Yasuo; Seino, Susumu; Lavstsen, Thomas; Hunziker, Walter

doi:10.1083/jcb.201304101

Cited by 15 publications

(22 citation statements)

References 76 publications

(109 reference statements)

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“…Our screen identified BARP and inositolrequiring enzyme-1α (IRE1α) as α6β4 enhancers. BARP is a single-pass transmembrane protein that was first identified in association with voltage-gated calcium channel β subunits (14) and was later found as an accessory component of α6β2β3 nAChRs (13), while IRE1α is a constituent of the unfolded protein response (UPR) (15). We found that the efficacy of nicotinic agonists to treat neuropathic pain best correlates with their activity on α6β4 receptors.…”

Section: Introductionmentioning

confidence: 92%

Functional α6β4 acetylcholine receptor expression enables pharmacological testing of nicotinic agonists with analgesic properties

Knowland¹,

Gu²,

Eckert³

et al. 2020

Journal of Clinical Investigation

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Section: Introductionmentioning

confidence: 92%

Functional α6β4 acetylcholine receptor expression enables pharmacological testing of nicotinic agonists with analgesic properties

Knowland¹,

Gu²,

Eckert³

et al. 2020

Journal of Clinical Investigation

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“…phosphorylation/ dephosphorylation, or after dissociation from a binding partner. A recent study suggests that BARP (β‐anchoring and ‐regulatory protein), a transmembrane protein expressed in the brain and in pancreas, could act as such a donor of β subunits (Beguin et al, ).…”

Section: Dynamic Subunit Composition Of Vgcc Complexesmentioning

confidence: 99%

The Role of Auxiliary Subunits for the Functional Diversity of Voltage‐Gated Calcium Channels

Campiglio

Flucher

2015

Journal Cellular Physiology

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Voltage-gated calcium channels (VGCCs) represent the sole mechanism to convert membrane depolarization into cellular functions like secretion, contraction, or gene regulation. VGCCs consist of a pore-forming α1 subunit and several auxiliary channel subunits. These subunits come in multiple isoforms and splice-variants giving rise to a stunning molecular diversity of possible subunit combinations. It is generally believed that specific auxiliary subunits differentially regulate the channels and thereby contribute to the great functional diversity of VGCCs. If auxiliary subunits can associate and dissociate from pre-existing channel complexes, this would allow dynamic regulation of channel properties. However, most auxiliary subunits modulate current properties very similarly, and proof that any cellular calcium channel function is indeed modulated by the physiological exchange of auxiliary subunits is still lacking. In this review we summarize available information supporting a differential modulation of calcium channel functions by exchange of auxiliary subunits, as well as experimental evidence in support of alternative functions of the auxiliary subunits. At the heart of the discussion is the concept that, in their native environment, VGCCs function in the context of macromolecular signaling complexes and that the auxiliary subunits help to orchestrate the diverse protein–protein interactions found in these calcium channel signalosomes. Thus, in addition to a putative differential modulation of current properties, differential subcellular targeting properties and differential protein–protein interactions of the auxiliary subunits may explain the need for their vast molecular diversity. J. Cell. Physiol. 999: 00–00, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. J. Cell. Physiol. 230: 2019–2031, 2015. © 2015 Wiley Periodicals, Inc.

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“…This integral membrane glycoprotein is predominantly expressed in neurons and neuropeptide secretory cells. In fact, high BARP mRNA levels were located in brain, pancreatic islets and neuroendocrine cell lines (MIN6 and PC12), with no or weak expression in other tissues [88]. Interestingly, in the brain and cerebellum, BARP co-immunoprecipitated with Ca v β 3 and Ca v β 4 but not with Ca v β 1 suggesting that BARP may associate with specific Ca v β in particular sub-cellular domains of neurons.…”

Section: Barp Negatively Regulates Vgcc Activity Via Ca V βmentioning

confidence: 89%

“…Thus, BARP controls the localization of Ca v β and its association with Ca v α 1 to negatively regulate VGCC activity. These findings may lead to new strategies for the design of original therapeutic VGCC blockers [88].…”

Section: Barp Negatively Regulates Vgcc Activity Via Ca V βmentioning

confidence: 98%

“…Internalization of VGCC and, consequently, a reduced number of channels at the plasma membrane [86] Ca v β 1 Slo1 Inhibits BK Ca channels Slows BK Ca channels activation/deactivation kinetics and decreases significantly their sensitivity to Ca 2+ [68] Ca v β 3 /Ca v β 4 BARP Negatively regulates VGCC activity BARP modulates the localization of Ca v β and its association with Ca v α 1 , thus inhibits Ca 2 + channel activity and Ca 2 + -evoked exocytosis [88] Ca v β 3 / Ca v β 4 Bestrophin-1 Regulates calcium channel function…”

Section: Actin the Most Recently Identified Partner Of Ca V βmentioning

confidence: 99%

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Protein partners of the calcium channel β subunit highlight new cellular functions

Rima

Daghsni

Fajloun

et al. 2016

Biochemical Journal

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Calcium plays a key role in cell signalling by its intervention in a wide range of physiological processes. Its entry into cells occurs mainly via voltage-gated calcium channels (VGCC), which are found not only in the plasma membrane of excitable cells but also in cells insensitive to electrical signals. VGCC are composed of different subunits, α1, β, α2δ and γ, among which the cytosolic β subunit (Cavβ) controls the trafficking of the channel to the plasma membrane, its regulation and its gating properties. For many years, these were the main functions associated with Cavβ. However, a growing number of proteins have been found to interact with Cavβ, emphasizing the multifunctional role of this versatile protein. Interestingly, some of the newly assigned functions of Cavβ are independent of its role in the regulation of VGCC, and thus further increase its functional roles. Based on the identity of Cavβ protein partners, this review emphasizes the diverse cellular functions of Cavβ and summarizes both past findings as well as recent progress in the understanding of VGCC.

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

Abstract: The integral membrane glycoprotein BARP associates with voltage-gated calcium channel Cavβ subunits, disrupting their association with Cavα1 subunits and suppressing overall channel activity.

Cited by 15 publications

References 76 publications

Functional α6β4 acetylcholine receptor expression enables pharmacological testing of nicotinic agonists with analgesic properties

Functional α6β4 acetylcholine receptor expression enables pharmacological testing of nicotinic agonists with analgesic properties

The Role of Auxiliary Subunits for the Functional Diversity of Voltage‐Gated Calcium Channels

Protein partners of the calcium channel β subunit highlight new cellular functions

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