Tags

Type your tag names separated by a space and hit enter

STIM1 regulates Ca2+ entry via arachidonate-regulated Ca2+-selective (ARC) channels without store depletion or translocation to the plasma membrane.
J Physiol. 2007 Mar 15; 579(Pt 3):703-15.JP

Abstract

Recent studies have indicated a critical role for STIM (stromal interacting molecule) proteins in the regulation of the store-operated mode of receptor-activated Ca2+ entry. Current models emphasize the role of STIM located in the endoplasmic reticulum membrane, where a Ca2+-binding EF-hand domain within the N-terminal of the protein lies within the lumen and is thought to represent the sensor for the depletion of intracellular Ca2+ stores. Dissociation of Ca2+ from this domain induces the aggregation of STIM to regions of the ER immediately adjacent to the plasma membrane where it acts to regulate the activity of store-operated Ca2+ channels. However, the possible effects of STIM on other modes of receptor-activated Ca2+ entry have not been examined. Here we show that STIM1 also regulates the arachidonic-acid-regulated Ca2+-selective (ARC) channels - receptor-activated Ca2+ entry channels whose activation is entirely independent of store depletion. Regulation of the ARC channels by STIM1 does not involve dissociation of Ca2+ from the EF-hand, or any translocation of STIM1. Instead, a critical role of STIM1 resident in the plasma membrane is indicated. Thus, exposure of intact cells to an antibody targeting the extracellular N-terminal domain of STIM1 inhibits ARC channel activity without significantly affecting the store-operated channels. A similar specific inhibition of the ARC channels is seen in cells expressing a STIM1 construct in which the N-linked glycosylation sites essential for the constitutive cell surface expression of STIM1, were mutated. We conclude that, in contrast to store-operated channels, regulation of ARC channels by STIM1 depends exclusively on the pool of STIM1 constitutively residing in the plasma membrane. These data demonstrate that STIM1 is a more universal regulator of Ca2+ entry pathways than previously thought, and appears to have multiple modes of action.

Authors+Show Affiliations

Department of Pharmacology and Physiology, Box 711, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17158173

Citation

Mignen, Olivier, et al. "STIM1 Regulates Ca2+ Entry Via Arachidonate-regulated Ca2+-selective (ARC) Channels Without Store Depletion or Translocation to the Plasma Membrane." The Journal of Physiology, vol. 579, no. Pt 3, 2007, pp. 703-15.
Mignen O, Thompson JL, Shuttleworth TJ. STIM1 regulates Ca2+ entry via arachidonate-regulated Ca2+-selective (ARC) channels without store depletion or translocation to the plasma membrane. J Physiol. 2007;579(Pt 3):703-15.
Mignen, O., Thompson, J. L., & Shuttleworth, T. J. (2007). STIM1 regulates Ca2+ entry via arachidonate-regulated Ca2+-selective (ARC) channels without store depletion or translocation to the plasma membrane. The Journal of Physiology, 579(Pt 3), 703-15.
Mignen O, Thompson JL, Shuttleworth TJ. STIM1 Regulates Ca2+ Entry Via Arachidonate-regulated Ca2+-selective (ARC) Channels Without Store Depletion or Translocation to the Plasma Membrane. J Physiol. 2007 Mar 15;579(Pt 3):703-15. PubMed PMID: 17158173.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - STIM1 regulates Ca2+ entry via arachidonate-regulated Ca2+-selective (ARC) channels without store depletion or translocation to the plasma membrane. AU - Mignen,Olivier, AU - Thompson,Jill L, AU - Shuttleworth,Trevor J, Y1 - 2006/12/07/ PY - 2006/12/13/pubmed PY - 2007/5/17/medline PY - 2006/12/13/entrez SP - 703 EP - 15 JF - The Journal of physiology JO - J Physiol VL - 579 IS - Pt 3 N2 - Recent studies have indicated a critical role for STIM (stromal interacting molecule) proteins in the regulation of the store-operated mode of receptor-activated Ca2+ entry. Current models emphasize the role of STIM located in the endoplasmic reticulum membrane, where a Ca2+-binding EF-hand domain within the N-terminal of the protein lies within the lumen and is thought to represent the sensor for the depletion of intracellular Ca2+ stores. Dissociation of Ca2+ from this domain induces the aggregation of STIM to regions of the ER immediately adjacent to the plasma membrane where it acts to regulate the activity of store-operated Ca2+ channels. However, the possible effects of STIM on other modes of receptor-activated Ca2+ entry have not been examined. Here we show that STIM1 also regulates the arachidonic-acid-regulated Ca2+-selective (ARC) channels - receptor-activated Ca2+ entry channels whose activation is entirely independent of store depletion. Regulation of the ARC channels by STIM1 does not involve dissociation of Ca2+ from the EF-hand, or any translocation of STIM1. Instead, a critical role of STIM1 resident in the plasma membrane is indicated. Thus, exposure of intact cells to an antibody targeting the extracellular N-terminal domain of STIM1 inhibits ARC channel activity without significantly affecting the store-operated channels. A similar specific inhibition of the ARC channels is seen in cells expressing a STIM1 construct in which the N-linked glycosylation sites essential for the constitutive cell surface expression of STIM1, were mutated. We conclude that, in contrast to store-operated channels, regulation of ARC channels by STIM1 depends exclusively on the pool of STIM1 constitutively residing in the plasma membrane. These data demonstrate that STIM1 is a more universal regulator of Ca2+ entry pathways than previously thought, and appears to have multiple modes of action. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/17158173/STIM1_regulates_Ca2+_entry_via_arachidonate_regulated_Ca2+_selective__ARC__channels_without_store_depletion_or_translocation_to_the_plasma_membrane_ L2 - https://doi.org/10.1113/jphysiol.2006.122432 DB - PRIME DP - Unbound Medicine ER -