Systems Biology Group, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110025, India.
Systems Biology Group, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110025, India.
Cell Calcium. 2018 Jan;69:19-27. doi: 10.1016/j.ceca.2017.06.002. Epub 2017 Jun 9.
Calcium (Ca) signaling plays a critical role in regulating plethora of cellular functions including cell survival, proliferation and migration. The perturbations in cellular Ca homeostasis can lead to cell death either by activating autophagic pathways or through induction of apoptosis. Endoplasmic reticulum (ER) is the major storehouse of Ca within cells and a number of physiological agonists mediate ER Ca release by activating IP receptors (IPR). This decrease in ER Ca levels is sensed by STIM, which physically interacts and activates plasma membrane Ca selective Orai channels. Emerging literature implicates a key role for STIM1, STIM2, Orai1 and Orai3 in regulating both cell survival and death pathways. In this review, we will retrospect the work highlighting the role of STIM and Orai homologs in regulating cell death signaling. We will further discuss the rationales that could explain the dual role of STIM and Orai proteins in regulating cell fate decisions.
钙（Ca）信号在调节细胞的多种功能中起着至关重要的作用，包括细胞存活、增殖和迁移。细胞内 Ca 稳态的紊乱可通过激活自噬途径或诱导细胞凋亡导致细胞死亡。内质网（ER）是细胞内 Ca 的主要储存库，许多生理激动剂通过激活 IP 受体（IPR）来介导 ER Ca 释放。内质网 Ca 水平的这种降低被 STIM 感知，STIM 通过与质膜 Ca 选择性 Orai 通道相互作用并激活它们来感知。越来越多的文献表明，STIM1、STIM2、Orai1 和 Orai3 在调节细胞存活和死亡途径方面起着关键作用。在这篇综述中，我们将回顾强调 STIM 和 Orai 同源物在调节细胞死亡信号中的作用的工作。我们将进一步讨论可以解释 STIM 和 Orai 蛋白在调节细胞命运决定中的双重作用的原理。
