STIM Is a Ca 2+ Sensor Essential for Ca 2+ -Store-Depletion-Triggered Ca 2+ Influx

Abstract

Summary ues (Figure 1B), the siRNAs targeting the gene productsSTIM (stromal interaction molecule) 1 and STIM2 stood Ca 2+ signaling in nonexcitable cells is typically initiated out in their ability to suppress the sustained Ca 2+ sig- by receptor-triggered production of inositol-1,4,5-tris- nals while showing little effect on the peak amplitude. phosphate and the release of Ca 2+ from intracellular Although STIM1 and STIM2 were identified previously stores [1]. An elusive signaling process senses the as potential tumor growth suppressors [8, 12, 13], they Ca 2+ store depletion and triggers the opening of had not been suspected of having a role in Ca 2+ signal- plasma membrane Ca 2+ channels [2–5]. The resulting ing. Nevertheless, both proteins have been biochemi- sustained Ca 2+ signals are required for many physio- cally characterized and have been shown to form ho- logical responses, such as T cell activation and differ- mo- and hetero-oligomers as well as to have a entiation [6]. Here, we monitored receptor-triggered