STIM1 and the noncapacitative ARC channels.

STIM1 and the noncapacitative ARC channels. Research Abstract Details 

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STIM1 and the noncapacitative ARC channels. Abstract Text:

Trevor J Shuttleworth,Jill L Thompson,Olivier Mignen,

Our understanding of the nature and regulation of receptor-activated Ca(2+) entry in nonexcitable cells has recently undergone a radical change that began with the identification of the stromal interacting molecule proteins (e.g., STIM1) as playing a critical role in the regulation of the capacitative, or store-operated, Ca(2+) entry. As such, current models emphasize the role of STIM1 located in the endoplasmic reticulum membrane, where it senses the status of the intracellular Ca(2+) stores via a luminal N-terminal Ca(2+)-binding EF-hand domain. Dissociation of Ca(2+) from this domain induces the clustering of STIM1 to regions of the ER that lie close to the plasma membrane, where it regulates the activity of the store-operated Ca(2+) channels (e.g., CRAC channels). Thus, the specific dependence on store-depletion, and the role of the Ca(2+)-binding EF-hand domain in this process, are critical to all current models of the action of STIM1 on Ca(2+) entry. However, until recently, the effects of STIM1 on other modes of receptor-activated Ca(2+) entry have not been examined. Surprisingly, we found that STIM1 exerts similar, although not identical, actions on the arachidonic acid-regulated Ca(2+)-selective (ARC) channels-a widely expressed mode of agonist-activated Ca(2+) entry whose activation is completely independent of Ca(2+) store depletion. Regulation of the ARC channels by STIM1 is not only independent of store depletion, but also of the Ca(2+)-binding function of the EF-hand, and translocation of STIM1 to the plasma membrane. Instead, it is the pool of STIM1 that constitutively resides in the plasma membrane that is critical for the regulation of the ARC channels. Thus, ARC channel activity is selectively inhibited by exposure of intact cells to an antibody targeting the extracellular N-terminal domain of STIM1. Similarly, introducing mutations in STIM1 that prevent the N-linked glycosylation-dependent constitutive expression of the protein in the plasma membrane specifically inhibits the activity of the ARC channels without affecting the CRAC channels. These studies demonstrate that STIM1 is a far more universal regulator of Ca(2+) entry pathways than previously assumed, and has multiple, and entirely distinct, modes of action. Precisely how this same protein can act in such separate and specific ways on these different pathways of agonist-activated Ca(2+)entry remains an intriguing, yet currently unresolved, question.

STIM1 and the noncapacitative ARC channels. Publishing Authors By Initials

TJ Shuttleworth,JL Thompson,O Mignen,

For similar proteins: neoplasm proteins research abstracts see: proteins: neoplasm proteins research

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STIM1 and the noncapacitative ARC channels. Journal Published:

PUBLICATION TYPE: Review

Journal: Cell calcium

VOLUME: 42

Page Numbers: 183-91

Journal Abbreviation: Cell Calcium

ISSN: 0143-4160

DAY: 27

MONTH: 03

YEAR: 2007

STIM1 and the noncapacitative ARC channels. Information

Number of References: 41

LANGUAGE: eng

NlmUniqueID: 8006226

STIM1 and the noncapacitative ARC channels. Keywords Mesh Terms:

KEYWORDS: Neoplasm Proteins

MESH TERMS: physiology

Chemical & Substance for Abstract: STIM1 and the noncapacitative ARC channels. Information

Substance Name: Arachidonic Acid

Registry Number: 506-32-1

Grant and Affiliation Information for STIM1 and the noncapacitative ARC channels.

AFFILIATION: Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA. trevor_shuttleworth@urmc.rochester.edu

Country: Scotland

AGENCY: United States NIGMS

GRANT: GM 040457

ACRONYM: GM

MEDLINETA: Cell Calcium

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