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Amplification of CRAC current by STIM1 and CRACM1 (Orai1)

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.

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Figure 1: Individual and combined overexpression of STIM1 and CRACM1.
Figure 2: Co-expression of CRACM1 and STIM1 produces a current with the characteristic features of ICRAC.

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References

  1. Roos, J. et al. J. Cell Biol. 169, 435–445 (2005).

    Article  CAS  Google Scholar 

  2. Zhang, S. L. et al. Nature 437, 902–905 (2005).

    Article  CAS  Google Scholar 

  3. Feske, S. et al. Nature 441, 179–185 (2006).

    Article  CAS  Google Scholar 

  4. Vig, M. et al. Science DOI: 10.1126/science.1127883 (2006).

  5. Hoth, M. & Penner, R. Nature 355, 353–356 (1992).

    Article  CAS  Google Scholar 

  6. Parekh, A. B. & Penner, R. Physiol. Rev. 77, 901–930 (1997).

    Article  CAS  Google Scholar 

  7. Parekh, A. B. & Putney, J. W., Jr. Physiol. Rev. 85, 757–810 (2005).

    Article  CAS  Google Scholar 

  8. Liou, J. et al. Curr. Biol. 15, 1235–1241 (2005).

    Article  CAS  Google Scholar 

  9. Spassova, M. A. et al. Proc. Natl Acad. Sci. USA 103, 4040–4045 (2006).

    Article  CAS  Google Scholar 

  10. Hoth, M. & Penner, R. J. Physiol. 465, 359–386 (1993).

    Article  CAS  Google Scholar 

  11. Zweifach, A. & Lewis, R. S. Proc. Natl Acad. Sci. USA 90, 6295–6299 (1993).

    Article  CAS  Google Scholar 

  12. Hoth, M. Pflugers Arch. 430, 315–322 (1995).

    Article  CAS  Google Scholar 

  13. Prakriya, M. & Lewis, R. S. J. Physiol. 536, 3–19 (2001).

    Article  CAS  Google Scholar 

  14. Hermosura, M. C., Monteilh-Zoller, M. K., Scharenberg, A. M., Penner, R. & Fleig, A. J. Physiol. 539, 445–458 (2002).

    Article  CAS  Google Scholar 

  15. Zweifach, A. & Lewis, R. S. J. Gen. Physiol. 107, 597–610 (1996).

    Article  CAS  Google Scholar 

Download references

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.).

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Correspondence to Reinhold Penner or Jean-Pierre Kinet.

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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.

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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

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