He, L., Wang, L., Zeng, H., Tan, P., Ma, G., Zheng, S., Li, Y., Sun, L., Dou, F., Siwko, S., Huang, Y., Wang, Y., Zhou, Y. (2021). Engineering of a bona fide light-operated calcium channel. Nat. Commun. 12(1): 164.
FlyBase ID
FBrf0247736
Publication Type
Research paper
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.
