Essential function for the calcium sensor STIM1 in mast cell activation and anaphylactic responses

Mast cells have key functions as effectors of immunoglobulin E-mediated allergic inflammatory diseases. Allergen stimulation induces Ca(2+) influx and elicits the secretion of inflammatory mediators from mast cells. Here we show that the Ca(2+)-binding endoplasmic reticulum protein STIM1 is critical to mast cell function. STIM1-deficient fetal liver-derived mast cells had impaired W, influx mediated by the high-affinity immunoglobulin E receptor Fc epsilon RI and activation of the transcription factors NF-kappa B and NFAT. Mast cells lacking STIM1 also had much less degranulation and cytokine production after Fc epsilon RI stimulation. In addition, alterations in STIM1 expression affected the sensitivity of immunoglobulin E-mediated immediate-phase anaphylactic responses in vivo. Thus, STIM1 is key in promoting the W, influx that is essential for Fc epsilon RI-mediated mast cell activation and anaphylaxis.