The STIM-Orai Pathway: Light-Operated Ca2+ Entry Through Engineered CRAC Channels

  • Guolin MaEmail author
  • Shufan Wen
  • Yun Huang
  • Yubin ZhouEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 993)


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.


Optogenetics 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.).


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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Center for Translational Cancer Research, Institute of Biosciences and TechnologyTexas A&M UniversityHoustonUSA
  2. 2.Center for Epigenetics and Disease Prevention, Institute of Biosciences and TechnologyTexas A&M UniversityHoustonUSA
  3. 3.Department of Medical Physiology, College of MedicineTexas A&M UniversityTempleUSA

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