More Than Just Simple Interaction between STIM and Orai Proteins: CRAC Channel Function Enabled by a Network of Interactions with Regulatory Proteins.
More Than Just Simple Interaction between STIM and Orai Proteins: CRAC Channel Function Enabled by a Network of Interactions with Regulatory Proteins.
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不仅仅是STIM和Orai蛋白之间的简单相互作用：与调节蛋白相互作用网络启用的CRAC通道功能。
DOI：
10.3390/ijms22010471
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发表时间：
2021-01-05
影响因子：
5.6
通讯作者：
Frischauf I
中科院分区：
文献类型：
--
作者：
Berlansky S;Humer C;Sallinger M;Frischauf I
钙释放激活的钙通道（CRAC）由内质网（ER）释放的Ca 2+激活，对于多种细胞类型中的Ca 2+稳态和活性信号转导至关重要。受长期寻求的CRAC通道的分子性质的解密的刺激，相当多的科学工作已经致力于深入了解这种信号级联的功能和结构机制。CRAC通道功能的关键参与者是基质相互作用分子1（STIM 1）和Orai 1。STIM 1蛋白跨越ER的膜，能够感测腔Ca 2+浓度，并且反过来负责将Ca 2+储存耗尽的信号传递给质膜中的孔形成Orai 1蛋白。STIM 1和Orai 1的直接相互作用允许Ca 2+从细胞外间隙重新进入。虽然我们已经对STIM 1和Orai 1的结构、功能和相互作用了解很多，但越来越多的证据表明，生理条件下的CRAC依赖于其他蛋白质才能正常发挥功能。几种辅助蛋白已显示通过与STIM 1和/或Orai 1直接相互作用来调节CRAC通道活性，以不同的机制方式促进或阻碍Ca 2+内流。还鉴定了多种蛋白质对CRAC信号级联发挥调节作用，尽管其本身缺乏对STIM 1和Orai 1的亲和力。除了普遍表达的代表，这样的调节机制的子集似乎允许CRAC通道功能的细胞类型特异性控制，考虑到特定蛋白质的相当有限的表达模式。鉴于通用和细胞类型特异性相互作用网络的高度功能和临床相关性，以下综述将提供多层CRAC通道信号级联调节剂的全面总结。它还包括在细胞和组织的窄谱中表达的蛋白质，这些蛋白质在类似主题的其他评论中经常被忽视。
The calcium-release-activated calcium (CRAC) channel, activated by the release of Ca2+ from the endoplasmic reticulum (ER), is critical for Ca2+ homeostasis and active signal transduction in a plethora of cell types. Spurred by the long-sought decryption of the molecular nature of the CRAC channel, considerable scientific effort has been devoted to gaining insights into functional and structural mechanisms underlying this signalling cascade. Key players in CRAC channel function are the Stromal interaction molecule 1 (STIM1) and Orai1. STIM1 proteins span through the membrane of the ER, are competent in sensing luminal Ca2+ concentration, and in turn, are responsible for relaying the signal of Ca2+ store-depletion to pore-forming Orai1 proteins in the plasma membrane. A direct interaction of STIM1 and Orai1 allows for the re-entry of Ca2+ from the extracellular space. Although much is already known about the structure, function, and interaction of STIM1 and Orai1, there is growing evidence that CRAC under physiological conditions is dependent on additional proteins to function properly. Several auxiliary proteins have been shown to regulate CRAC channel activity by means of direct interactions with STIM1 and/or Orai1, promoting or hindering Ca2+ influx in a mechanistically diverse manner. Various proteins have also been identified to exert a modulatory role on the CRAC signalling cascade although inherently lacking an affinity for both STIM1 and Orai1. Apart from ubiquitously expressed representatives, a subset of such regulatory mechanisms seems to allow for a cell-type-specific control of CRAC channel function, considering the rather restricted expression patterns of the specific proteins. Given the high functional and clinical relevance of both generic and cell-type-specific interacting networks, the following review shall provide a comprehensive summary of regulators of the multilayered CRAC channel signalling cascade. It also includes proteins expressed in a narrow spectrum of cells and tissues that are often disregarded in other reviews of similar topics.
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影响因子：
4.6
作者：
Albarran L;Lopez JJ;Amor NB;Martin-Cano FE;Berna-Erro A;Smani T;Salido GM;Rosado JA
通讯作者：
Rosado JA
影响因子：
4
作者：
Cao X;Choi S;Maléth JJ;Park S;Ahuja M;Muallem S
通讯作者：
Muallem S
影响因子：
16.6
作者：
Deb BK;Pathak T;Hasan G
通讯作者：
Hasan G
影响因子：
--
作者：
Albarran, Letizia;Lopez, Jose J.;Rosado, Juan A.
通讯作者：
Rosado, Juan A.
DOI：
10.1016/j.bbamcr.2015.02.014
发表时间：
2015-05-01
影响因子：
5.1
作者：
Dionisio, Natalia;Smani, Tarik;Rosado, Juan A.
通讯作者：
Rosado, Juan A.