Institute of Biochemistry and Molecular Medicine, National Center of Competence in Research NCCR TransCure, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland.
Burgweg 8, 53424 Remagen, Germany.
Semin Cell Dev Biol. 2019 Oct;94:66-73. doi: 10.1016/j.semcdb.2019.01.003. Epub 2019 Jan 12.
Precise intracellular calcium signaling is crucial to numerous cellular functions. In non-excitable cells, store-operated calcium entry (SOCE) is a key step in the generation of intracellular calcium signals. Tight regulation of SOCE is important, and dysregulation is involved in several pathophysiological cellular malfunctions. The current underlying SOCE, calcium release-activated calcium current (I), was first discovered almost three decades ago. Since its discovery, the molecular components of I, Orai1 and stromal interaction molecule 1 (STIM1), have been extensively investigated. Several regulatory mechanisms and proteins contribute to alterations in SOCE and cellular malfunctions in cancer, immune and neurodegenerative diseases, inflammation, and neuronal disorders. This review summarizes these regulatory mechanisms, including glycosylation, pH sensing, and the regulatory proteins golli, α-SNAP, SARAF, ORMDL3, CRACR2A, and TRPM4 channels.
精确的细胞内钙信号对于许多细胞功能至关重要。在非兴奋细胞中，储存操纵的钙内流（SOCE）是产生细胞内钙信号的关键步骤。SOCE 的严格调节很重要，失调与几种病理生理细胞功能障碍有关。目前的基础 SOCE，钙释放激活钙电流（I），在近三十年前首次发现。自发现以来，I 的分子成分，Orai1 和基质相互作用分子 1（STIM1），已经得到了广泛的研究。几种调节机制和蛋白有助于改变 SOCE 和癌症、免疫和神经退行性疾病、炎症以及神经元紊乱中的细胞功能障碍。这篇综述总结了这些调节机制，包括糖基化、pH 感应以及调节蛋白 golli、α-SNAP、SARAF、ORMDL3、CRACR2A 和 TRPM4 通道。
