The STIM-Orai Pathway: Light-Operated Ca2+ Entry Through Engineered CRAC Channels
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Ca2+ signals regulate a plethora of cellular functions that include muscle contraction, heart beating, hormone secretion, lymphocyte activation, gene expression, and metabolism. To study the impact of Ca2+ signals on biological processes, pharmacological tools and caged compounds have been commonly applied to induce fluctuations of intracellular Ca2+ concentrations. These conventional approaches, nonetheless, lack rapid reversibility and high spatiotemporal resolution. To overcome these disadvantages, we and others have devised a series of photoactivatable genetically encoded Ca2+ actuators (GECAs) by installing light sensitivities into a bona fide highly selective Ca2+ channel, the Ca2+ release-activated Ca2+ (CRAC) channel. Store-operated CRAC channel serves as a major route for Ca2+ entry in many cell types. These GECAs enable remote and precise manipulation of Ca2+ signaling in both excitable and non-excitable cells. When combined with nanotechnology, it becomes feasible to wirelessly photo-modulate Ca2+-dependent activities in vivo. In this chapter, we briefly review most recent advances in engineering CRAC channels to achieve optical control over Ca2+ signaling, outline their design principles and kinetic features, and present exemplary applications of GECAs engineered from CRAC channels.
KeywordsOptogenetics Calcium release-activated calcium (CRAC) channel Immune response STIM1 LOV2 Cryptochrome
This work was supported by grants from the Welch Foundation (BE-1913 to Y.Z.), the American Cancer Society (RSG-16-215-01-TBE to Y.Z.), and the National Institutes of Health (R01GM112003 to Y.Z.).
- Jing J, He L, Sun A, Quintana A, Ding Y, Ma G, Tan P, Liang X, Zheng X, Chen L, Shi X, Zhang SL, Zhong L, Huang Y, Dong MQ, Walker CL, Hogan PG, Wang Y, Zhou Y (2015) Proteomic mapping of ER-PM junctions identifies STIMATE as a regulator of Ca(2)(+) influx. Nat Cell Biol 17:1339–1347CrossRefPubMedPubMedCentralGoogle Scholar
- Stathopulos PB, Ikura M (2016) Store operated calcium entry: from concept to structural mechanisms. Cell Calcium. PMID: 27914753, doi: 10.1016/j.ceca.2016.11.005