Engineering of a bona fide light-operated calcium channel
Lian He,
Liuqing Wang,
Hongxiang Zeng,
Peng Tan,
Guolin Ma,
Sisi Zheng,
Yaxin Li,
Lin Sun,
Fei Dou,
Stefan Siwko,
Yun Huang (),
Youjun Wang () and
Yubin Zhou ()
Additional contact information
Lian He: Texas A&M University
Liuqing Wang: College of Life Sciences, Beijing Normal University
Hongxiang Zeng: Texas A&M University
Peng Tan: Texas A&M University
Guolin Ma: Texas A&M University
Sisi Zheng: College of Life Sciences, Beijing Normal University
Yaxin Li: College of Life Sciences, Beijing Normal University
Lin Sun: College of Life Sciences, Beijing Normal University
Fei Dou: College of Life Sciences, Beijing Normal University
Stefan Siwko: Texas A&M University
Yun Huang: Texas A&M University
Youjun Wang: College of Life Sciences, Beijing Normal University
Yubin Zhou: Texas A&M University
Nature Communications, 2021, vol. 12, issue 1, 1-11
Abstract:
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.
Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20425-4
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DOI: 10.1038/s41467-020-20425-4
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