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Properties of Orai1 mediated store-operated current depend on the expression levels of STIM1 and Orai1 proteins.
J Physiol. 2009 Jun 15; 587(Pt 12):2903-18.JP

Abstract

Two cellular proteins, stromal interaction molecule 1 (STIM1) and Orai1, are recently discovered essential components of the Ca2+ release activated Ca2+ (CRAC) channel. Orai1 polypeptides form the pore of the CRAC channel, while STIM1 plays the role of the endoplasmic reticulum Ca2+ sensor required for activation of CRAC current (I(CRAC)) by store depletion. It is not known, however, if the role of STIM1 is limited exclusively to Ca2+ sensing, or whether interaction between Orai1 and STIM1, either direct or indirect, also defines the properties of I(CRAC). In this study we investigated how the relative expression levels of ectopic Orai1 and STIM1 affect the properties of I(CRAC). The results show that cells expressing low Orai1 : STIM1 ratios produce I(CRAC) with strong fast Ca2+-dependent inactivation, while cells expressing high Orai1 : STIM1 ratios produce I(CRAC) with strong activation at negative potentials. Moreover, the expression ratio of Orai1 and STIM1 affects Ca2+, Ba2+ and Sr2+ conductance, but has no effect on the current in the absence of divalent cations. The results suggest that several key properties of Ca2+ channels formed by Orai1 depend on its interaction with STIM1, and that the stoichiometry of this interaction may vary depending on the relative expression levels of these proteins.

Authors+Show Affiliations

School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19403622

Citation

Scrimgeour, N, et al. "Properties of Orai1 Mediated Store-operated Current Depend On the Expression Levels of STIM1 and Orai1 Proteins." The Journal of Physiology, vol. 587, no. Pt 12, 2009, pp. 2903-18.
Scrimgeour N, Litjens T, Ma L, et al. Properties of Orai1 mediated store-operated current depend on the expression levels of STIM1 and Orai1 proteins. J Physiol. 2009;587(Pt 12):2903-18.
Scrimgeour, N., Litjens, T., Ma, L., Barritt, G. J., & Rychkov, G. Y. (2009). Properties of Orai1 mediated store-operated current depend on the expression levels of STIM1 and Orai1 proteins. The Journal of Physiology, 587(Pt 12), 2903-18. https://doi.org/10.1113/jphysiol.2009.170662
Scrimgeour N, et al. Properties of Orai1 Mediated Store-operated Current Depend On the Expression Levels of STIM1 and Orai1 Proteins. J Physiol. 2009 Jun 15;587(Pt 12):2903-18. PubMed PMID: 19403622.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Properties of Orai1 mediated store-operated current depend on the expression levels of STIM1 and Orai1 proteins. AU - Scrimgeour,N, AU - Litjens,T, AU - Ma,L, AU - Barritt,G J, AU - Rychkov,G Y, Y1 - 2009/04/29/ PY - 2009/5/1/entrez PY - 2009/5/1/pubmed PY - 2009/9/22/medline SP - 2903 EP - 18 JF - The Journal of physiology JO - J Physiol VL - 587 IS - Pt 12 N2 - Two cellular proteins, stromal interaction molecule 1 (STIM1) and Orai1, are recently discovered essential components of the Ca2+ release activated Ca2+ (CRAC) channel. Orai1 polypeptides form the pore of the CRAC channel, while STIM1 plays the role of the endoplasmic reticulum Ca2+ sensor required for activation of CRAC current (I(CRAC)) by store depletion. It is not known, however, if the role of STIM1 is limited exclusively to Ca2+ sensing, or whether interaction between Orai1 and STIM1, either direct or indirect, also defines the properties of I(CRAC). In this study we investigated how the relative expression levels of ectopic Orai1 and STIM1 affect the properties of I(CRAC). The results show that cells expressing low Orai1 : STIM1 ratios produce I(CRAC) with strong fast Ca2+-dependent inactivation, while cells expressing high Orai1 : STIM1 ratios produce I(CRAC) with strong activation at negative potentials. Moreover, the expression ratio of Orai1 and STIM1 affects Ca2+, Ba2+ and Sr2+ conductance, but has no effect on the current in the absence of divalent cations. The results suggest that several key properties of Ca2+ channels formed by Orai1 depend on its interaction with STIM1, and that the stoichiometry of this interaction may vary depending on the relative expression levels of these proteins. SN - 1469-7793 UR - https://www.unboundmedicine.com/medline/citation/19403622/Properties_of_Orai1_mediated_store_operated_current_depend_on_the_expression_levels_of_STIM1_and_Orai1_proteins_ L2 - https://doi.org/10.1113/jphysiol.2009.170662 DB - PRIME DP - Unbound Medicine ER -