STIM1 is required for attenuation of PMCA-mediated Ca2+ clearance during T-cell activation

T-cell activation involves a complex signalling cascade uniquely dependent on elevated cytosolic Ca2+ levels. Further, the spatiotemporal characteristics of this Ca2+ signal play a critical role in this process via selective activation of transcription factors. In T cells, store-operated Ca2+ entry (SOCe) is the primary Ca2+ influx pathway; however, cytosolic Ca2+ concentration depends upon the balance between Ca2+ influx and extrusion. The plasma membrane Ca2+ ATPase (PMCA) has previously been identified as a critical player in Ca2+ clearance in T cells. Here, we provide data revealing both functional and physical links between the activation of stromal interacting molecule 1 (STIM1) and PMCA-mediated Ca2+ clearance. Due to the ubiquitous expression of both STIM1 and PMCA, these findings have wide-ranging implications for Ca2+ signalling in multiple cell types. The EMBO Journal (2012) 31, 1123-1133. doi: 10.1038/emboj.2011.495; Published online 13 January 2012