STIM1 is a Ca2+ Sensor That Activates CRAC Channels and Migrates from the Ca2+ Store to the Plasma Membrane

Authors

Shenyuan L. ZhangFollow
Ying YuFollow
Jack Roos
J. Ashot Kozak, Wright State University - Main CampusFollow
Thomas J. Deerinck
Mark H. Ellisman
Kenneth A. Stauderman
Michael D. Cahalan

Document Type

Article

Publication Date

10-6-2005

Abstract

As the sole Ca²⁺ entry mechanism in a variety of non-excitable cells, store-operated calcium (SOC) influx plays an important role in Ca²⁺ signaling and many other cellular processes^1–3. A calcium release-activated calcium (CRAC) channel in T lymphocytes is the best characterized SOC influx channel^4–6 and is essential to the immune response, sustained activity of CRAC channels being required for gene expression and proliferation^7–10. The molecular identity and the gating mechanism of SOC and CRAC channels have remained elusive. Previously, we identified Stim and the mammalian homolog STIM1 as essential components of CRAC channel activation in Drosophila S2 cells and human T lymphocytes¹¹. Here, we show that 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 demonstrate that STIM1 migrates from ER-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.

Repository Citation

Zhang, S. L., Yu, Y., Roos, J., Kozak, J. A., Deerinck, T. J., Ellisman, M. H., Stauderman, K. A., & Cahalan, M. D. (2005). STIM1 is a Ca2+ Sensor That Activates CRAC Channels and Migrates from the Ca2+ Store to the Plasma Membrane. Nature, 437 (7060), 902-905.
https://corescholar.libraries.wright.edu/ncbp/134

DOI

10.1038/nature04147