Pumped out to activate
As a regulator of many facets of cellular activity, the concentration of cytosolic calcium ions (Ca2+) is tightly controlled by pumps and channels in organelles and the plasma membrane. An influx of Ca2+ to the cytosol triggers various signaling pathways. Curiously, Go et al. found that the Ca2+ extrusion pump PMCA4 in the plasma membrane promoted, rather than inhibited, the Ca2+-induced activation of T cells. PMCA4-mediated clearance of membrane-proximal Ca2+ pools triggered endoplasmic reticulum–resident Ca2+ sensor/channel duo STIM1/Orai1 to release stored Ca2+, thereby activating an immune response–associated transcription factor in cultured T cells. These findings reveal a coupling between a plasma membrane Ca2+ pump and an organellar Ca2+ storage machinery.
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