Role of Alpha-SNAP in Store-Operated Calcium Entry, Lymphocyte Activation and...

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Sustained Ca2+ signaling is crucial for lymphocyte activation and effector functions. Store-operated calcium release activated calcium (CRAC) channels play a major role in sustaining calcium signaling in lymphocytes. Previously, we identified the gene encoding CRAC channels as CRACM1 (also known as Orail). CRAC channel deficiency results in severe defects in cytokine secretion in lymphocytes and degranulation in mast cells. Point mutations in CRACMI/Orail have been associated with immune-deficiency in human patients. ST1M1 is a crucial regulator of CRAC channels. However, the precise details of how ST1M1 regulates SOCE through CRAC channels remains unknown. Our genome-wide RNAi screen to identify molecular players involved in SOCE identified SNAP (soluble NSF attachment protein) as an important regulator of SOCE in drosophila S2 cells. RNAi mediated knockdown of alpha-SNAP, the mammalian ortholog of SNAP inhibits SOCE in HEK-293 cells. Here, we propose to understand the regulation of SOCE by alpha-SNAP using the following approach.