Optogenetic engineering to probe the molecular choreography of STIM1-mediated cell signaling

Guolin Ma, Lian He, Shuzhong Liu, Jiansheng Xie, Zixian Huang, Ji Jing, Yi-Tsang Lee, Rui Wang, Hesheng Luo, Weidong Han (), Yun Huang () and Yubin Zhou ()
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Guolin Ma: Texas A&M University
Lian He: Texas A&M University
Shuzhong Liu: Texas A&M University
Jiansheng Xie: Texas A&M University
Zixian Huang: Texas A&M University
Ji Jing: Texas A&M University
Yi-Tsang Lee: Texas A&M University
Rui Wang: Texas A&M University
Hesheng Luo: Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University
Weidong Han: Zhejiang University
Yun Huang: Texas A&M University
Yubin Zhou: Texas A&M University

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Genetically encoded photoswitches have enabled spatial and temporal control of cellular events to achieve tailored functions in living cells, but their applications to probe the structure-function relations of signaling proteins are still underexplored. We illustrate herein the incorporation of various blue light-responsive photoreceptors into modular domains of the stromal interaction molecule 1 (STIM1) to manipulate protein activity and faithfully recapitulate STIM1-mediated signaling events. Capitalizing on these optogenetic tools, we identify the molecular determinants required to mediate protein oligomerization, intramolecular conformational switch, and protein-target interactions. In parallel, we have applied these synthetic devices to enable light-inducible gating of calcium channels, conformational switch, dynamic protein-microtubule interactions and assembly of membrane contact sites in a reversible manner. Our optogenetic engineering approach can be broadly applied to aid the mechanistic dissection of cell signaling, as well as non-invasive interrogation of physiological processes with high precision.

Date: 2020
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DOI: 10.1038/s41467-020-14841-9

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