CRAC channel-based optogenetics.
CRAC channel-based optogenetics.
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DOI：
10.1016/j.ceca.2018.08.007
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发表时间：
2018-11
期刊：
影响因子：
4
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Nguyen NT;Ma G;Lin E;D'Souza B;Jing J;He L;Huang Y;Zhou Y
钙池操纵的钙内流（SOCE）是哺乳动物体内钙内流的主要途径，参与调节肌肉收缩、突触传递、基因表达和代谢等多种生理过程。在非兴奋性细胞中，由奥赖和基质相互作用分子（STIM）组成的Ca 2+释放激活的Ca 2+（CRAC）通道代表了SOCE介导内质网（ER）和质膜（PM）之间的特化膜接触位点（MCS）处的Ca 2+进入的原型实例。SOCE激活的关键步骤包括在Ca 2+储存耗尽时ER驻留的Ca 2+传感器STIM 1的管腔结构域的寡聚化，随后的信号向胞质结构域传播以触发构象转换并克服分子内自抑制，以及最小的ORAI激活结构域的最终暴露以直接接合并门控质膜中的奥赖通道。这种精细协调的细胞事件也由STIM 1的C-末端多碱基结构域促进，其与嵌入PM内小叶中的带负电荷的磷酸肌醇物理缔合，以使STIM 1能够有效易位到ER-PM MCS中。在这里，我们提出了最近的进展，重演STIM 1介导的SOCE激活工程CRAC通道与光遗传学的方法。这些基于STIM 1的光遗传学工具不仅可以机械地重新捕获SOCE激活的关键分子步骤，而且还可以远程和可逆地控制Ca 2+依赖性细胞过程，MCS的细胞器间束缚，以及与基于CRISPR/Cas9的基因组编辑工具相结合时的转录重编程。
Store-operated Ca2+ entry (SOCE) constitutes a major Ca2+ influx pathway in mammals to regulate a myriad of physiological processes, including muscle contraction, synaptic transmission, gene expression, and metabolism. In non-excitable cells, the Ca2+ release-activated Ca2+ (CRAC) channel, composed of ORAI and stromal interaction molecule (STIM), represents a prototypical example of SOCE to mediate Ca2+ entry at specialized membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and the plasma membrane (PM). The key steps of SOCE activation include the oligomerization of the luminal domain of the ER-resident Ca2+ sensor STIM1 upon Ca2+ store depletion, subsequent signal propagation toward the cytoplasmic domain to trigger a conformational switch and overcome the intramolecular autoinhibition, and ultimate exposure of the minimal ORAI-activating domain to directly engage and gate ORAI channels in the plasma membrane. This exquisitely coordinated cellular event is also facilitated by the C-terminal polybasic domain of STIM1, which physically associates with negatively charged phosphoinositides embedded in the inner leaflet of the PM to enable efficient translocation of STIM1 into ER-PM MCSs. Here, we present recent progress in recapitulating STIM1-mediated SOCE activation by engineering CRAC channels with optogenetic approaches. These STIM1-based optogenetic tools make it possible to not only mechanistically recapture the key molecular steps of SOCE activation, but also remotely and reversibly control Ca2+-dependent cellular processes, inter-organellar tethering at MCSs, and transcriptional reprogramming when combined with CRISPR/Cas9-based genome-editing tools.
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影响因子：
8.7
作者：
通讯作者：
--
影响因子：
13.9
作者：
Fenno L;Yizhar O;Deisseroth K
通讯作者：
Deisseroth K
DOI：
10.1126/science.aah3404
发表时间：
2016-12-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
Hahn KM
DOI：
10.1073/pnas.1503191112
发表时间：
2015-04-21
影响因子：
11.1
作者：
Fernandez-Busnadiego, Ruben;Saheki, Yasunori;De Camilli, Pietro
通讯作者：
De Camilli, Pietro
影响因子：
4.8
作者：
Frischauf, Irene;Muik, Martin;Romanin, Christoph
通讯作者：
Romanin, Christoph