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

持续的钙信号对淋巴细胞的激活和效应器功能至关重要。钙释放激活钙通道(CRAC)在维持淋巴细胞钙信号中起着重要作用。 此前，我们鉴定了编码CRAC通道的基因为CRACM1(也称为ORAIL)。CRAC通道缺陷导致淋巴细胞分泌细胞因子的严重缺陷和肥大细胞脱颗粒。CRACMI/ORAIL基因的点突变与人类患者的免疫缺陷有关。 ST1M1是CRAC通道的重要调节因子。然而，ST1M1如何通过CRAC通道调节SOCE的确切细节仍不清楚。我们的全基因组RNAi筛查确定了参与SOCE的分子分子SNAP(可溶性NSF附着蛋白)是SOCE的重要调节因子。 果蝇S2细胞。RNAi介导的哺乳动物同源SNAPα-SNAP抑制HEK-293细胞SOCE。在这里，我们建议使用以下方法来理解α-SNAP对SOCE的调节。

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.