STIM is a Ca2+ sensor essential for Ca2+-store- depletion-triggered Ca2+ influx

Jen Liou, Man Lyang Kim, Do Heo Won, Joshua T. Jones, Jason W. Myers, James E. Ferrell, Tobias Meyer

Research output: Contribution to journalArticlepeer-review

1765 Scopus citations


Ca2+ signaling in nonexcitable cells is typically initiated by receptor-triggered production of inositol-1,4,5-trisphosphate and the release of Ca2+ from intracellular stores [1]. An elusive signaling process senses the Ca2+ store depletion and triggers the opening of plasma membrane Ca2+ channels [2-5]. The resulting sustained Ca2+ signals are required for many physiological responses, such as T cell activation and differentiation [6]. Here, we monitored receptor-triggered Ca2+ signals in cells transfected with siRNAs against 2,304 human signaling proteins, and we identified two proteins required for Ca 2+-store-depletion-mediated Ca2+ influx, STIM1 and STIM2 [7-9]. These proteins have a single transmembrane region with a putative Ca 2+ binding domain in the lumen of the endoplasmic reticulum. Ca 2+ store depletion led to a rapid translocation of STIM1 into puncta that accumulated near the plasma membrane. Introducing a point mutation in the STIM1 Ca2+ binding domain resulted in prelocalization of the protein in puncta, and this mutant failed to respond to store depletion. Our study suggests that STIM proteins function as Ca2+ store sensors in the signaling pathway connecting Ca2+ store depletion to Ca2+ influx.

Original languageEnglish (US)
Pages (from-to)1235-1241
Number of pages7
JournalCurrent Biology
Issue number13
StatePublished - Jul 12 2005

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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