Abstract
Depletion of intracellular calcium stores activates store-operated calcium entry across the plasma membrane in many cells. STIM1, the putative calcium sensor in the endoplasmic reticulum, and the calcium release-activated calcium (CRAC) modulator CRACM1 (also known as Orai1) in the plasma membrane have recently been shown to be essential for controlling the store-operated CRAC current (ICRAC)1,2,3,4. However, individual overexpression of either protein fails to significantly amplify ICRAC. Here, we show that STIM1 and CRACM1 interact functionally. Overexpression of both proteins greatly potentiates ICRAC, suggesting that STIM1 and CRACM1 mutually limit store-operated currents and that CRACM1 may be the long-sought CRAC channel.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Roos, J. et al. J. Cell Biol. 169, 435–445 (2005).
Zhang, S. L. et al. Nature 437, 902–905 (2005).
Feske, S. et al. Nature 441, 179–185 (2006).
Vig, M. et al. Science DOI: 10.1126/science.1127883 (2006).
Hoth, M. & Penner, R. Nature 355, 353–356 (1992).
Parekh, A. B. & Penner, R. Physiol. Rev. 77, 901–930 (1997).
Parekh, A. B. & Putney, J. W., Jr. Physiol. Rev. 85, 757–810 (2005).
Liou, J. et al. Curr. Biol. 15, 1235–1241 (2005).
Spassova, M. A. et al. Proc. Natl Acad. Sci. USA 103, 4040–4045 (2006).
Hoth, M. & Penner, R. J. Physiol. 465, 359–386 (1993).
Zweifach, A. & Lewis, R. S. Proc. Natl Acad. Sci. USA 90, 6295–6299 (1993).
Hoth, M. Pflugers Arch. 430, 315–322 (1995).
Prakriya, M. & Lewis, R. S. J. Physiol. 536, 3–19 (2001).
Hermosura, M. C., Monteilh-Zoller, M. K., Scharenberg, A. M., Penner, R. & Fleig, A. J. Physiol. 539, 445–458 (2002).
Zweifach, A. & Lewis, R. S. J. Gen. Physiol. 107, 597–610 (1996).
Acknowledgements
We thank M. Bellinger for help with cell culture. This work was supported, in part, by National Institutes of Health (NIH) grants 5-R37-GM053950 (to J.P.K.), R01-AI050200 and R01-NS040927 (to R.P.) and R01-GM065360 (to A.F.).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
J.P.K., R.P., A.F. and M.N. are consultants to Synta Pharmaceuticals Corp. (Lexington, MA). J.P.K. and R.P. are members of the scientific advisory board of Synta Pharmaceuticals Corp.
Supplementary information
Supplementary Information
Supplementary Figures S1, S2 and Supplementary Methods (PDF 293 kb)
Rights and permissions
About this article
Cite this article
Peinelt, C., Vig, M., Koomoa, D. et al. Amplification of CRAC current by STIM1 and CRACM1 (Orai1). Nat Cell Biol 8, 771–773 (2006). https://doi.org/10.1038/ncb1435
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ncb1435
This article is cited by
-
Pharmacological inhibitors of the cystic fibrosis transmembrane conductance regulator exert off-target effects on epithelial cation channels
Pflügers Archiv - European Journal of Physiology (2023)
-
Orai1α, but not Orai1β, co-localizes with TRPC1 and is required for its plasma membrane location and activation in HeLa cells
Cellular and Molecular Life Sciences (2022)
-
Beta-Glycerophosphate-Induced ORAI1 Expression and Store Operated Ca2+ Entry in Megakaryocytes
Scientific Reports (2020)
-
Decreased Na+/K+ ATPase Expression and Depolarized Cell Membrane in Neurons Differentiated from Chorea-Acanthocytosis Patients
Scientific Reports (2020)
-
Stimulation of ORAI1 expression, store-operated Ca2+ entry, and osteogenic signaling by high glucose exposure of human aortic smooth muscle cells
Pflügers Archiv - European Journal of Physiology (2020)