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Optogenetic engineering to probe the molecular choreography of STIM1-mediated cell signaling
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Optogenetic engineering to probe the molecular choreography of STIM1-mediated cell signaling
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Journal Article
Optogenetic engineering to probe the molecular choreography of STIM1-mediated cell signaling
2020
Overview
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.
Optogenetic tools have been used to control cellular behaviours but their use to probe structure-function relations of signalling proteins are underexplored. Here the authors engineer optogenetic modules into STIM1 to dissect molecular details of STIM1-mediated signalling and control various cellular events.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/35
/ 14/63
/ 49/47
/ 96/95
/ Arabidopsis Proteins - genetics
/ Bacterial Proteins - genetics
/ High-Throughput Nucleotide Sequencing
/ Humanities and Social Sciences
/ Humans
/ Luminescent Proteins - genetics
/ Mutation
/ Neoplasm Proteins - chemistry
/ Neoplasm Proteins - genetics
/ Neoplasm Proteins - metabolism
/ Protein Engineering - methods
/ Proteins
/ Recombinant Proteins - genetics
/ Recombinant Proteins - metabolism
/ Science
/ Stromal Interaction Molecule 1 - chemistry
/ Stromal Interaction Molecule 1 - genetics
/ Stromal Interaction Molecule 1 - metabolism
