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Store-dependent and -independent modes regulating Ca2+ release-activated Ca2+ channel activity of human Orai1 and Orai3.
J Biol Chem. 2008 Jun 20; 283(25):17662-71.JB

Abstract

We evaluated currents induced by expression of human homologs of Orai together with STIM1 in human embryonic kidney cells. When co-expressed with STIM1, Orai1 induced a large inwardly rectifying Ca(2+)-selective current with Ca(2+)-induced slow inactivation. A point mutation of Orai1 (E106D) altered the ion selectivity of the induced Ca(2+) release-activated Ca(2+) (CRAC)-like current while retaining an inwardly rectifying I-V characteristic. Expression of the C-terminal portion of STIM1 with Orai1 was sufficient to generate CRAC current without store depletion. 2-APB activated a large relatively nonselective current in STIM1 and Orai3 co-expressing cells. 2-APB also induced Ca(2+) influx in Orai3-expressing cells without store depletion or co-expression of STIM1. The Orai3 current induced by 2-APB exhibited outward rectification and an inward component representing a mixed calcium and monovalent current. A pore mutant of Orai3 inhibited store-operated Ca(2+) entry and did not carry significant current in response to either store depletion or addition of 2-APB. Analysis of a series of Orai1-3 chimeras revealed the structural determinant responsible for 2-APB-induced current within the sequence from the second to third transmembrane segment of Orai3. The Orai3 current induced by 2-APB may reflect a store-independent mode of CRAC channel activation that opens a relatively nonselective cation pore.

Authors+Show Affiliations

Department of Physiology and Biophysics, University of California, Irvine, California 92697, USA.No affiliation info availableNo affiliation info availableNo 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

18420579

Citation

Zhang, Shenyuan L., et al. "Store-dependent and -independent Modes Regulating Ca2+ Release-activated Ca2+ Channel Activity of Human Orai1 and Orai3." The Journal of Biological Chemistry, vol. 283, no. 25, 2008, pp. 17662-71.
Zhang SL, Kozak JA, Jiang W, et al. Store-dependent and -independent modes regulating Ca2+ release-activated Ca2+ channel activity of human Orai1 and Orai3. J Biol Chem. 2008;283(25):17662-71.
Zhang, S. L., Kozak, J. A., Jiang, W., Yeromin, A. V., Chen, J., Yu, Y., Penna, A., Shen, W., Chi, V., & Cahalan, M. D. (2008). Store-dependent and -independent modes regulating Ca2+ release-activated Ca2+ channel activity of human Orai1 and Orai3. The Journal of Biological Chemistry, 283(25), 17662-71. https://doi.org/10.1074/jbc.M801536200
Zhang SL, et al. Store-dependent and -independent Modes Regulating Ca2+ Release-activated Ca2+ Channel Activity of Human Orai1 and Orai3. J Biol Chem. 2008 Jun 20;283(25):17662-71. PubMed PMID: 18420579.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Store-dependent and -independent modes regulating Ca2+ release-activated Ca2+ channel activity of human Orai1 and Orai3. AU - Zhang,Shenyuan L, AU - Kozak,J Ashot, AU - Jiang,Weihua, AU - Yeromin,Andriy V, AU - Chen,Jing, AU - Yu,Ying, AU - Penna,Aubin, AU - Shen,Wei, AU - Chi,Victor, AU - Cahalan,Michael D, Y1 - 2008/04/17/ PY - 2008/4/19/pubmed PY - 2008/7/26/medline PY - 2008/4/19/entrez SP - 17662 EP - 71 JF - The Journal of biological chemistry JO - J Biol Chem VL - 283 IS - 25 N2 - We evaluated currents induced by expression of human homologs of Orai together with STIM1 in human embryonic kidney cells. When co-expressed with STIM1, Orai1 induced a large inwardly rectifying Ca(2+)-selective current with Ca(2+)-induced slow inactivation. A point mutation of Orai1 (E106D) altered the ion selectivity of the induced Ca(2+) release-activated Ca(2+) (CRAC)-like current while retaining an inwardly rectifying I-V characteristic. Expression of the C-terminal portion of STIM1 with Orai1 was sufficient to generate CRAC current without store depletion. 2-APB activated a large relatively nonselective current in STIM1 and Orai3 co-expressing cells. 2-APB also induced Ca(2+) influx in Orai3-expressing cells without store depletion or co-expression of STIM1. The Orai3 current induced by 2-APB exhibited outward rectification and an inward component representing a mixed calcium and monovalent current. A pore mutant of Orai3 inhibited store-operated Ca(2+) entry and did not carry significant current in response to either store depletion or addition of 2-APB. Analysis of a series of Orai1-3 chimeras revealed the structural determinant responsible for 2-APB-induced current within the sequence from the second to third transmembrane segment of Orai3. The Orai3 current induced by 2-APB may reflect a store-independent mode of CRAC channel activation that opens a relatively nonselective cation pore. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/18420579/Store_dependent_and__independent_modes_regulating_Ca2+_release_activated_Ca2+_channel_activity_of_human_Orai1_and_Orai3_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)81670-6 DB - PRIME DP - Unbound Medicine ER -