STIM and Orai Mediated Regulation of Calcium Signaling in Age-Related Diseases.
STIM and Orai Mediated Regulation of Calcium Signaling in Age-Related Diseases.
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DOI：
10.3389/fragi.2022.876785
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发表时间：
2022
影响因子：
--
通讯作者：
Chatham, John C.
中科院分区：
文献类型：
--
作者：
Collins, Helen E.;Zhang, Dingguo;Chatham, John C.
细胞内Ca 2+的严格时空调节在调节包括细胞存活、代谢和转录在内的多种细胞功能中起关键作用。因此，真核细胞已经开发出多种机制来控制Ca 2+跨质膜流入和流出以及从细胞内储存释放和摄取Ca 2+。STIM和奥赖蛋白家族由STIM 1、STIM 2、Orai 1、Orai 2和Orai 3组成，是进化上高度保守的蛋白，是所有哺乳动物Ca 2+信号系统的核心组分。STIM 1和Orai 1被认为是调控钙库操纵的钙内流（SOCE）的关键参与者，其中Ca 2+从细胞内储存（如内质网/肌浆网（ER/SR））释放触发Ca 2+跨质膜内流。SOCE在非兴奋细胞中广泛存在，在Ca 2+依赖的转录调控中起着重要作用。除了在Ca 2+信号传导中的作用外，STIM 1和Orai 1还被证明有助于调节代谢和线粒体功能。STIM和奥赖蛋白也受到氧化还原修饰，这影响它们的活性。考虑到它们的普遍表达，人们对STIM和奥赖蛋白在可兴奋细胞如神经元和肌细胞中的作用越来越感兴趣。虽然关于SOCE在可兴奋细胞中的重要性仍存在争议，但STIM 1和Orai 1对细胞稳态至关重要，它们的破坏与各种与衰老相关的疾病有关，如心血管疾病和神经退行性疾病。最近发现的大多数STIM和奥赖亚型的剪接变体虽然使我们对其功能的理解变得复杂，但也可能为目前对其作用的一些矛盾提供见解。因此，本次审查的目的是描述我们目前的理解的分子调控的STIM和奥赖蛋白和它们的作用在正常生理和疾病的老化，特别是心脏病和神经退行性疾病。
Tight spatiotemporal regulation of intracellular Ca2+ plays a critical role in regulating diverse cellular functions including cell survival, metabolism, and transcription. As a result, eukaryotic cells have developed a wide variety of mechanisms for controlling Ca2+ influx and efflux across the plasma membrane as well as Ca2+ release and uptake from intracellular stores. The STIM and Orai protein families comprising of STIM1, STIM2, Orai1, Orai2, and Orai3, are evolutionarily highly conserved proteins that are core components of all mammalian Ca2+ signaling systems. STIM1 and Orai1 are considered key players in the regulation of Store Operated Calcium Entry (SOCE), where release of Ca2+ from intracellular stores such as the Endoplasmic/Sarcoplasmic reticulum (ER/SR) triggers Ca2+ influx across the plasma membrane. SOCE, which has been widely characterized in non-excitable cells, plays a central role in Ca2+-dependent transcriptional regulation. In addition to their role in Ca2+ signaling, STIM1 and Orai1 have been shown to contribute to the regulation of metabolism and mitochondrial function. STIM and Orai proteins are also subject to redox modifications, which influence their activities. Considering their ubiquitous expression, there has been increasing interest in the roles of STIM and Orai proteins in excitable cells such as neurons and myocytes. While controversy remains as to the importance of SOCE in excitable cells, STIM1 and Orai1 are essential for cellular homeostasis and their disruption is linked to various diseases associated with aging such as cardiovascular disease and neurodegeneration. The recent identification of splice variants for most STIM and Orai isoforms while complicating our understanding of their function, may also provide insight into some of the current contradictions on their roles. Therefore, the goal of this review is to describe our current understanding of the molecular regulation of STIM and Orai proteins and their roles in normal physiology and diseases of aging, with a particular focus on heart disease and neurodegeneration.
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影响因子：
20.3
作者：
Braun, Attila;Varga-Szabo, David;Nieswandt, Bernhard
通讯作者：
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影响因子：
5.6
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7.5
作者：
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通讯作者：
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作者：
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