Institute for Health Promotion Research, Department of Population Health Sciences, UT Health San Antonio, San Antonio, TX 78229, USA.
Department of Periodontics, School of Dentistry, University of Texas Health Science Center, 7703 Floyd Curl Drive, Mail Code 7763, San Antonio, TX 78229, USA.
Cells. 2021 Aug 18;10(8):2125. doi: 10.3390/cells10082125.
Calcium (Ca) functions as a second messenger that is critical in regulating fundamental physiological functions such as cell growth/development, cell survival, neuronal development and/or the maintenance of cellular functions. The coordination among various proteins/pumps/Ca channels and Ca storage in various organelles is critical in maintaining cytosolic Ca levels that provide the spatial resolution needed for cellular homeostasis. An important regulatory aspect of Ca homeostasis is a store operated Ca entry (SOCE) mechanism that is activated by the depletion of Ca from internal ER stores and has gained much attention for influencing functions in both excitable and non-excitable cells. Ca has been shown to regulate opposing functions such as autophagy, that promote cell survival; on the other hand, Ca also regulates programmed cell death processes such as apoptosis. The functional significance of the TRP/Orai channels has been elaborately studied; however, information on how they can modulate opposing functions and modulate function in excitable and non-excitable cells is limited. Importantly, perturbations in SOCE have been implicated in a spectrum of pathological neurodegenerative conditions. The critical role of autophagy machinery in the pathogenesis of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases, would presumably unveil avenues for plausible therapeutic interventions for these diseases. We thus review the role of SOCE-regulated Ca signaling in modulating these diverse functions in stem cell, immune regulation and neuromodulation.
钙 (Ca) 作为一种第二信使，在调节细胞生长/发育、细胞存活、神经元发育和/或细胞功能维持等基本生理功能中起着关键作用。各种蛋白质/泵/Ca 通道之间的协调以及各种细胞器中的 Ca 储存对于维持细胞内环境稳定所需的胞质 Ca 水平至关重要。Ca 稳态的一个重要调节方面是由内质网 (ER) 内部储存的 Ca 耗竭激活的储存操纵性 Ca 内流 (SOCE) 机制，该机制已引起广泛关注，影响兴奋和非兴奋细胞的功能。Ca 已被证明可以调节相反的功能，如促进细胞存活的自噬；另一方面，Ca 还调节程序性细胞死亡过程，如细胞凋亡。TRP/Orai 通道的功能意义已经得到了详细的研究；然而，关于它们如何调节相反的功能以及调节兴奋和非兴奋细胞的功能的信息有限。重要的是，SOCE 的扰动与一系列病理性神经退行性疾病有关。自噬机制在阿尔茨海默病、帕金森病和亨廷顿病等神经退行性疾病的发病机制中的关键作用，可能会为这些疾病的合理治疗干预提供途径。因此，我们综述了 SOCE 调节的 Ca 信号在调节干细胞、免疫调节和神经调节中的这些不同功能中的作用。
