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Engineering of a bona fide light-operated calcium channel.


ABSTRACT: The current optogenetic toolkit lacks a robust single-component Ca2+-selective ion channel tailored for remote control of Ca2+ signaling in mammals. Existing tools are either derived from engineered channelrhodopsin variants without strict Ca2+ selectivity or based on the stromal interaction molecule 1 (STIM1) that might crosstalk with other targets. Here, we describe the design of a light-operated Ca2+ channel (designated LOCa) by inserting a plant-derived photosensory module into the intracellular loop of an engineered ORAI1 channel. LOCa displays biophysical features reminiscent of the ORAI1 channel, which enables precise optical control over Ca2+ signals and hallmark Ca2+-dependent physiological responses. Furthermore, we demonstrate the use of LOCa to modulate aberrant hematopoietic stem cell self-renewal, transcriptional programming, cell suicide, as well as neurodegeneration in a Drosophila model of amyloidosis.

SUBMITTER: He L 

PROVIDER: S-EPMC7801460 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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The current optogenetic toolkit lacks a robust single-component Ca<sup>2+</sup>-selective ion channel tailored for remote control of Ca<sup>2+</sup> signaling in mammals. Existing tools are either derived from engineered channelrhodopsin variants without strict Ca<sup>2+</sup> selectivity or based on the stromal interaction molecule 1 (STIM1) that might crosstalk with other targets. Here, we describe the design of a light-operated Ca<sup>2+</sup> channel (designated LOCa) by inserting a plant-de  ...[more]

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