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

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.