doi:10.12202/j.0476-0301.2021039王刘清¹,
何涟²,
孙林^1,,
王友军^1,,
1.北京师范大学生命科学学院遗传与发育所，抗性基因资源与分子发育北京市重点实验室，100875，北京
2.?Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA
基金项目:国家自然科学基金重大研究计划资助项目（91954205）

详细信息

通讯作者:王友军（1975-），男，教授，博士生导师. 研究方向：钙信号机制. E-mail：wyoujun@bnu.edu.cn

中图分类号:Q71

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出版历程

收稿日期:2021-01-26
网络出版日期:2021-01-21
刊出日期:2021-05-08

Development of a light-switchable Orai1 channel and its applications in the drosophila model of Alzheimer’s disease

Liuqing WANG¹,
Lian HE²,
Lin SUN^1,,
Youjun WANG^1,,
1. Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, China
2. Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA



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Abstract:As important regulators of cell function, CRAC channels have been implicated in a myriad of human disorders．Optogenetic tools provide opportunities to remotely and noninvasively control CRAC channels with high spatiotemporal precision and rapid reversibility．However, the application of existing optogenetic toolkits is impeded by some drawbacks, such as absolute requirement of endogenous ORAI channels or easily crosstalk with other targets．To overcome these hurdles, we introduce a single-component, blue-light operated calcium channel (LOCa) by directly installing the LOV2 photoswitch into engineered Orai1 channels．Similar to CRAC channels, LOCa is highly selective for Ca²⁺．Without the need for extra cofactors, LOCa enables optical control of Ca²⁺ influx in a reversible manner．We applied LOCa to maintain the self-renewal of hematopoietic stem cells (HSCs), and established the feasibility of alleviating neurodegeneration syndromes with light in a drosophila model of amyloidosis, showing its potential as a novel interventional approach for CRAC related diseases．