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

J Liou, ML Kim, W Do Heo, JT Jones, JW Myers… - Current biology, 2005 - cell.com
J Liou, ML Kim, W Do Heo, JT Jones, JW Myers, JE Ferrell, T Meyer
Current biology, 2005cell.com
Ca 2+ signaling in nonexcitable cells is typically initiated by receptor-triggered production of
inositol-1, 4, 5-trisphosphate and the release of Ca 2+ from intracellular stores [1]. An elusive
signaling process senses the Ca 2+ store depletion and triggers the opening of plasma
membrane Ca 2+ channels [2–5]. The resulting sustained Ca 2+ signals are required for
many physiological responses, such as T cell activation and differentiation [6]. Here, we
monitored receptor-triggered Ca 2+ signals in cells transfected with siRNAs against 2,304 …
Summary
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 Ca2+-store-depletion-mediated Ca2+ influx, STIM1 and STIM2 [7–9]. These proteins have a single transmembrane region with a putative Ca2+ binding domain in the lumen of the endoplasmic reticulum. Ca2+ 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.
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