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STIM2 is an inhibitor of STIM1-mediated store-operated Ca2+ Entry.
Curr Biol. 2006 Jul 25; 16(14):1465-70.CB

Abstract

The coupling mechanism between endoplasmic reticulum (ER) Ca(2+) stores and plasma membrane (PM) store-operated channels (SOCs) remains elusive [1-3]. STIM1 was shown to play a crucial role in this coupling process [4-7]; however, the role of the closely related STIM2 protein remains undetermined. We reveal that STIM2 is a powerful SOC inhibitor when expressed in HEK293, PC12, A7r5, and Jurkat T cells. This contrasts with gain of SOC function in STIM1-expressing cells. While STIM1 is expressed in both the ER and plasma membrane, STIM2 is expressed only intracellularly. Store depletion induces redistribution of STIM1 into distinct "puncta." STIM2 translocates into puncta upon store depletion only when coexpressed with STIM1. Double labeling shows coincidence of STIM1 and STIM2 within puncta, and immunoprecipitation reveals direct interactions between STIM1 and STIM2. Independent of store depletion, STIM2 colocalizes with and blocks the function of a STIM1 EF-hand mutant that preexists in puncta and is constitutively coupled to activate SOCs. Thus, whereas STIM1 is a required mediator of SOC activation, STIM2 is a powerful inhibitor of this process, interfering with STIM1-mediated SOC activation at a point downstream of puncta formation. The opposing functions of STIM1 and STIM2 suggest they may play a coordinated role in controlling SOC-mediated Ca(2+) entry signals.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, 21201, USA. jsobo001@umaryland.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

16860747

Citation

Soboloff, Jonathan, et al. "STIM2 Is an Inhibitor of STIM1-mediated Store-operated Ca2+ Entry." Current Biology : CB, vol. 16, no. 14, 2006, pp. 1465-70.
Soboloff J, Spassova MA, Hewavitharana T, et al. STIM2 is an inhibitor of STIM1-mediated store-operated Ca2+ Entry. Curr Biol. 2006;16(14):1465-70.
Soboloff, J., Spassova, M. A., Hewavitharana, T., He, L. P., Xu, W., Johnstone, L. S., Dziadek, M. A., & Gill, D. L. (2006). STIM2 is an inhibitor of STIM1-mediated store-operated Ca2+ Entry. Current Biology : CB, 16(14), 1465-70.
Soboloff J, et al. STIM2 Is an Inhibitor of STIM1-mediated Store-operated Ca2+ Entry. Curr Biol. 2006 Jul 25;16(14):1465-70. PubMed PMID: 16860747.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - STIM2 is an inhibitor of STIM1-mediated store-operated Ca2+ Entry. AU - Soboloff,Jonathan, AU - Spassova,Maria A, AU - Hewavitharana,Thamara, AU - He,Li-Ping, AU - Xu,Wen, AU - Johnstone,Lorna S, AU - Dziadek,Marie A, AU - Gill,Donald L, PY - 2006/02/01/received PY - 2006/05/23/revised PY - 2006/05/24/accepted PY - 2006/7/25/pubmed PY - 2006/9/21/medline PY - 2006/7/25/entrez SP - 1465 EP - 70 JF - Current biology : CB JO - Curr Biol VL - 16 IS - 14 N2 - The coupling mechanism between endoplasmic reticulum (ER) Ca(2+) stores and plasma membrane (PM) store-operated channels (SOCs) remains elusive [1-3]. STIM1 was shown to play a crucial role in this coupling process [4-7]; however, the role of the closely related STIM2 protein remains undetermined. We reveal that STIM2 is a powerful SOC inhibitor when expressed in HEK293, PC12, A7r5, and Jurkat T cells. This contrasts with gain of SOC function in STIM1-expressing cells. While STIM1 is expressed in both the ER and plasma membrane, STIM2 is expressed only intracellularly. Store depletion induces redistribution of STIM1 into distinct "puncta." STIM2 translocates into puncta upon store depletion only when coexpressed with STIM1. Double labeling shows coincidence of STIM1 and STIM2 within puncta, and immunoprecipitation reveals direct interactions between STIM1 and STIM2. Independent of store depletion, STIM2 colocalizes with and blocks the function of a STIM1 EF-hand mutant that preexists in puncta and is constitutively coupled to activate SOCs. Thus, whereas STIM1 is a required mediator of SOC activation, STIM2 is a powerful inhibitor of this process, interfering with STIM1-mediated SOC activation at a point downstream of puncta formation. The opposing functions of STIM1 and STIM2 suggest they may play a coordinated role in controlling SOC-mediated Ca(2+) entry signals. SN - 0960-9822 UR - https://www.unboundmedicine.com/medline/citation/16860747/STIM2_is_an_inhibitor_of_STIM1_mediated_store_operated_Ca2+_Entry_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-9822(06)01634-4 DB - PRIME DP - Unbound Medicine ER -