STIM1 is required for attenuation of PMCA-mediated Ca 2+ clearance during T-cell activation

Abstract

T-cell activation involves a complex signalling cascade uniquely dependent on elevated cytosolic Ca 2+ levels. Further, the spatiotemporal characteristics of this Ca 2+ signal play a critical role in this process via selective activation of transcription factors. In T cells, store-operated Ca 2+ entry (SOCe) is the primary Ca 2+ influx pathway; however, cytosolic Ca 2+ concentration depends upon the balance between Ca 2+ influx and extrusion. The plasma membrane Ca 2+ ATPase (PMCA) has previously been identified as a critical player in Ca 2+ 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 Ca 2+ clearance. Due to the ubiquitous expression of both STIM1 and PMCA, these findings have wide-ranging implications for Ca 2+ signalling in multiple cell types. © 2012 European Molecular Biology Organization | All Rights Reserved.