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STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane

Author

Listed:
  • Shenyuan L. Zhang

    (University of California)

  • Ying Yu

    (University of California)

  • Jack Roos

    (TorreyPines Therapeutics, Inc.)

  • J. Ashot Kozak

    (University of California)

  • Thomas J. Deerinck

    (University of California, San Diego)

  • Mark H. Ellisman

    (University of California, San Diego)

  • Kenneth A. Stauderman

    (TorreyPines Therapeutics, Inc.)

  • Michael D. Cahalan

    (University of California)

Abstract

As the sole Ca2+ entry mechanism in a variety of non-excitable cells, store-operated calcium (SOC) influx is important in Ca2+ signalling and many other cellular processes1,2,3. A calcium-release-activated calcium (CRAC) channel in T lymphocytes is the best-characterized SOC influx channel4,5,6 and is essential to the immune response, sustained activity of CRAC channels being required for gene expression and proliferation7,8,9,10. The molecular identity and the gating mechanism of SOC and CRAC channels have remained elusive. Previously we identified Stim and the mammalian homologue STIM1 as essential components of CRAC channel activation in Drosophila S2 cells and human T lymphocytes11. Here we show that the expression of EF-hand mutants of Stim or STIM1 activates CRAC channels constitutively without changing Ca2+ store content. By immunofluorescence, EM localization and surface biotinylation we show that STIM1 migrates from endoplasmic-reticulum-like sites to the plasma membrane upon depletion of the Ca2+ store. We propose that STIM1 functions as the missing link between Ca2+ store depletion and SOC influx, serving as a Ca2+ sensor that translocates upon store depletion to the plasma membrane to activate CRAC channels.

Suggested Citation

  • Shenyuan L. Zhang & Ying Yu & Jack Roos & J. Ashot Kozak & Thomas J. Deerinck & Mark H. Ellisman & Kenneth A. Stauderman & Michael D. Cahalan, 2005. "STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane," Nature, Nature, vol. 437(7060), pages 902-905, October.
    • Handle: RePEc:nat:nature:v:437:y:2005:i:7060:d:10.1038_nature04147
    DOI: 10.1038/nature04147
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    Cited by:

    1. Lena Maltan & Sarah Weiß & Hadil Najjar & Melanie Leopold & Sonja Lindinger & Carmen Höglinger & Lorenz Höbarth & Matthias Sallinger & Herwig Grabmayr & Sascha Berlansky & Denis Krivic & Valentina Hop, 2023. "Photocrosslinking-induced CRAC channel-like Orai1 activation independent of STIM1," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Junjun Gao & Song Zhang & Pan Deng & Zhigang Wu & Bruno Lemaitre & Zongzhao Zhai & Zheng Guo, 2024. "Dietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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