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Orai1 and STIM reconstitute store-operated calcium channel function.
J Biol Chem. 2006 Jul 28; 281(30):20661-5.JB

Abstract

The two membrane proteins, STIM1 and Orai1, have each been shown to be essential for the activation of store-operated channels (SOC). Yet, how these proteins functionally interact is not known. Here, we reveal that STIM1 and Orai1 expressed together reconstitute functional SOCs. Expressed alone, Orai1 strongly reduces store-operated Ca(2+) entry (SOCE) in human embryonic kidney 293 cells and the Ca(2+) release-activated Ca(2+) current (I(CRAC)) in rat basophilic leukemia cells. However, expressed along with the store-sensing STIM1 protein, Orai1 causes a massive increase in SOCE, enhancing the rate of Ca(2+)entry by up to 103-fold. This entry is entirely store-dependent since the same coexpression causes no measurable store-independent Ca(2+) entry. The entry is completely blocked by the SOC blocker, 2-aminoethoxydiphenylborate. Orai1 and STIM1 coexpression also caused a large gain in CRAC channel function in rat basophilic leukemia cells. The close STIM1 homologue, STIM2, inhibited SOCE when expressed alone but coexpressed with Orai1 caused substantial constitutive (store-independent) Ca(2+) entry. STIM proteins are known to mediate Ca(2+) store-sensing and endoplasmic reticulum-plasma membrane coupling with no intrinsic channel properties. Our results revealing a powerful gain in SOC function dependent on the presence of both Orai1 and STIM1 strongly suggest that Orai1 contributes the PM channel component responsible for Ca(2+) entry. The suppression of SOC function by Orai1 overexpression likely reflects a required stoichiometry between STIM1 and Orai1.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, 21201, USA.No 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

16766533

Citation

Soboloff, Jonathan, et al. "Orai1 and STIM Reconstitute Store-operated Calcium Channel Function." The Journal of Biological Chemistry, vol. 281, no. 30, 2006, pp. 20661-5.
Soboloff J, Spassova MA, Tang XD, et al. Orai1 and STIM reconstitute store-operated calcium channel function. J Biol Chem. 2006;281(30):20661-5.
Soboloff, J., Spassova, M. A., Tang, X. D., Hewavitharana, T., Xu, W., & Gill, D. L. (2006). Orai1 and STIM reconstitute store-operated calcium channel function. The Journal of Biological Chemistry, 281(30), 20661-5.
Soboloff J, et al. Orai1 and STIM Reconstitute Store-operated Calcium Channel Function. J Biol Chem. 2006 Jul 28;281(30):20661-5. PubMed PMID: 16766533.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Orai1 and STIM reconstitute store-operated calcium channel function. AU - Soboloff,Jonathan, AU - Spassova,Maria A, AU - Tang,Xiang D, AU - Hewavitharana,Thamara, AU - Xu,Wen, AU - Gill,Donald L, Y1 - 2006/06/09/ PY - 2006/6/13/pubmed PY - 2006/9/19/medline PY - 2006/6/13/entrez SP - 20661 EP - 5 JF - The Journal of biological chemistry JO - J Biol Chem VL - 281 IS - 30 N2 - The two membrane proteins, STIM1 and Orai1, have each been shown to be essential for the activation of store-operated channels (SOC). Yet, how these proteins functionally interact is not known. Here, we reveal that STIM1 and Orai1 expressed together reconstitute functional SOCs. Expressed alone, Orai1 strongly reduces store-operated Ca(2+) entry (SOCE) in human embryonic kidney 293 cells and the Ca(2+) release-activated Ca(2+) current (I(CRAC)) in rat basophilic leukemia cells. However, expressed along with the store-sensing STIM1 protein, Orai1 causes a massive increase in SOCE, enhancing the rate of Ca(2+)entry by up to 103-fold. This entry is entirely store-dependent since the same coexpression causes no measurable store-independent Ca(2+) entry. The entry is completely blocked by the SOC blocker, 2-aminoethoxydiphenylborate. Orai1 and STIM1 coexpression also caused a large gain in CRAC channel function in rat basophilic leukemia cells. The close STIM1 homologue, STIM2, inhibited SOCE when expressed alone but coexpressed with Orai1 caused substantial constitutive (store-independent) Ca(2+) entry. STIM proteins are known to mediate Ca(2+) store-sensing and endoplasmic reticulum-plasma membrane coupling with no intrinsic channel properties. Our results revealing a powerful gain in SOC function dependent on the presence of both Orai1 and STIM1 strongly suggest that Orai1 contributes the PM channel component responsible for Ca(2+) entry. The suppression of SOC function by Orai1 overexpression likely reflects a required stoichiometry between STIM1 and Orai1. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/16766533/Orai1_and_STIM_reconstitute_store_operated_calcium_channel_function_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=16766533 DB - PRIME DP - Unbound Medicine ER -