Abstract
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.
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References
Banerjee R, Schleicher E, Meier S, Viana RM, Pokorny R, Ahmad M, Bittl R, Batschauer A (2007) The signaling state of Arabidopsis cryptochrome 2 contains flavin semiquinone. J Biol Chem 282:14916–14922
Berridge MJ, Bootman MD, Lipp P (1998) Calcium—a life and death signal. Nature 395:645–648
Berridge MJ, Lipp P, Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1:11–21
Cahalan MD, Zhang SL, Yeromin AV, Ohlsen K, Roos J, Stauderman KA (2007) Molecular basis of the CRAC channel. Cell Calcium 42:133–144
Cao X, Choi S, Maleth JJ, Park S, Ahuja M, Muallem S (2015) The ER/PM microdomain, PI(4,5)P(2) and the regulation of STIM1-Orai1 channel function. Cell Calcium 58:342–348
Chang CL, Liou J (2016) Homeostatic regulation of the PI(4,5)P2-Ca(2+) signaling system at ER-PM junctions. Biochim Biophys Acta 1861:862–873
Chen G, Qiu H, Prasad PN, Chen X (2014) Upconversion nanoparticles: design, nanochemistry, and applications in theranostics. Chem Rev 114:5161–5214
Deisseroth K (2011) Optogenetics. Nat Methods 8:26–29
Deisseroth K (2015) Optogenetics: 10 years of microbial opsins in neuroscience. Nat Neurosci 18:1213–1225
Derler I, Jardin I, Stathopulos PB, Muik M, Fahrner M, Zayats V, Pandey SK, Poteser M, Lackner B, Absolonova M, Schindl R, Groschner K, Ettrich R, Ikura M, Romanin C (2016) Cholesterol modulates orai1 channel function. Sci Signal 9(412):ra10
Fahrner M, Muik M, Schindl R, Butorac C, Stathopulos P, Zheng L, Jardin I, Ikura M, Romanin C (2014) A coiled-coil clamp controls both conformation and clustering of stromal interaction molecule 1 (STIM1). J Biol Chem 289:33231–33244
Fenno L, Yizhar O, Deisseroth K (2011) The development and application of optogenetics. Annu Rev Neurosci 34:389–412
Feske S (2007) Calcium signalling in lymphocyte activation and disease. Nat Rev Immunol 7:690–702
Feske S, Prakriya M (2013) Conformational dynamics of STIM1 activation. Nat Struct Mol Biol 20:918–919
Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A (2006) A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441:179–185
Feske S, Wulff H, Skolnik EY (2015) Ion channels in innate and adaptive immunity. Annu Rev Immunol 33:291–353
Giovani B, Byrdin M, Ahmad M, Brettel K (2003) Light-induced electron transfer in a cryptochrome blue-light photoreceptor. Nat Struct Biol 10:489–490
Harper SM, Neil LC, Gardner KH (2003) Structural basis of a phototropin light switch. Science 301:1541–1544
He L, Zhang Y, Ma G, Tan P, Li Z, Zang S, Wu X, Jing J, Fang S, Zhou L, Wang Y, Huang Y, Hogan PG, Han G, Zhou Y (2015) Near-infrared photoactivatable control of Ca(2+) signaling and optogenetic immunomodulation. eLife 4:e10024
Hogan PG, Lewis RS, Rao A (2010) Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. Annu Rev Immunol 28:491–533
Hooper R, Soboloff J (2015) STIMATE reveals a STIM1 transitional state. Nat Cell Biol 17:1232–1234
Huala E, Oeller PW, Liscum E, Han IS, Larsen E, Briggs WR (1997) Arabidopsis NPH1: a protein kinase with a putative redox-sensing domain. Science 278:2120–2123
Idevall-Hagren O, Dickson EJ, Hille B, Toomre DK, De Camilli P (2012) Optogenetic control of phosphoinositide metabolism. Proc Natl Acad Sci U S A 109:E2316–E2323
Ishii T, Sato K, Kakumoto T, Miura S, Touhara K, Takeuchi S, Nakata T (2015) Light generation of intracellular Ca(2+) signals by a genetically encoded protein BACCS. Nat Commun 6:8021
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 17:1339–1347
Kakumoto T, Nakata T (2013) Optogenetic control of PIP3: PIP3 is sufficient to induce the actin-based active part of growth cones and is regulated via endocytosis. PLoS One 8:e70861
Kawasaki T, Lange I, Feske S (2009) A minimal regulatory domain in the C terminus of STIM1 binds to and activates ORAI1 CRAC channels. Biochem Biophys Res Commun 385:49–54
Kennedy MJ, Hughes RM, Peteya LA, Schwartz JW, Ehlers MD, Tucker CL (2010) Rapid blue-light-mediated induction of protein interactions in living cells. Nat Methods 7:973–975
Kianianmomeni A (2015) UVB-based optogenetic tools. Trends Biotechnol 33:59–61
Kim N, Kim JM, Lee M, Kim CY, Chang KY, Heo WD (2014) Spatiotemporal control of fibroblast growth factor receptor signals by blue light. Chem Biol 21:903–912
Kondoh M, Shiraishi C, Muller P, Ahmad M, Hitomi K, Getzoff ED, Terazima M (2011) Light-induced conformational changes in full-length Arabidopsis thaliana cryptochrome. J Mol Biol 413:128–137
Kyung T, Lee S, Kim JE, Cho T, Park H, Jeong YM, Kim D, Shin A, Kim S, Baek J, Kim J, Kim NY, Woo D, Chae S, Kim CH, Shin HS, Han YM, Kim D, Heo WD (2015) Optogenetic control of endogenous Ca(2+) channels in vivo. Nat Biotechnol 33:1092–1096
Lacruz RS, Feske S (2015) Diseases caused by mutations in ORAI1 and STIM1. Ann N Y Acad Sci 1356:45–79
LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155–184
Lee S, Park H, Kyung T, Kim NY, Kim S, Kim J, Heo WD (2014) Reversible protein inactivation by optogenetic trapping in cells. Nat Methods 11:633–636
Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE Jr, Meyer T (2005) STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol 15:1235–1241
Luik RM, Wang B, Prakriya M, Wu MM, Lewis RS (2008) Oligomerization of STIM1 couples ER calcium depletion to CRAC channel activation. Nature 454:538–542
Ma G, Wei M, He L, Liu C, Wu B, Zhang SL, Jing J, Liang X, Senes A, Tan P, Li S, Sun A, Bi Y, Zhong L, Si H, Shen Y, Li M, Lee MS, Zhou W, Wang J, Wang Y, Zhou Y (2015) Inside-out Ca(2+) signalling prompted by STIM1 conformational switch. Nat Commun 6:7826
Maleth J, Choi S, Muallem S, Ahuja M (2014) Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating. Nat Commun 5:5843
Muik M, Fahrner M, Derler I, Schindl R, Bergsmann J, Frischauf I, Groschner K, Romanin C (2009) A cytosolic homomerization and a modulatory domain within STIM1 C terminus determine coupling to ORAI1 channels. J Biol Chem 284:8421–8426
Muik M, Fahrner M, Schindl R, Stathopulos P, Frischauf I, Derler I, Plenk P, Lackner B, Groschner K, Ikura M, Romanin C (2011) STIM1 couples to ORAI1 via an intramolecular transition into an extended conformation. EMBO J 30:1678–1689
Nihongaki Y, Yamamoto S, Kawano F, Suzuki H, Sato M (2015) CRISPR-Cas9-based photoactivatable transcription system. Chem Biol 22:169–174
Pacheco J, Dominguez L, Bohorquez-Hernandez A, Asanov A, Vaca L (2016) A cholesterol-binding domain in STIM1 modulates STIM1-Orai1 physical and functional interactions. Sci Rep 6:29634
Parekh AB, Putney JW Jr (2005) Store-operated calcium channels. Physiol Rev 85:757–810
Park CY, Hoover PJ, Mullins FM, Bachhawat P, Covington ED, Raunser S, Walz T, Garcia KC, Dolmetsch RE, Lewis RS (2009) STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. Cell 136:876–890
Park H, Lee S, Heo WD (2016) Protein inactivation by optogenetic trapping in living cells. Methods Mol Biol 1408:363–376
Pathak GP, Vrana JD, Tucker CL (2013) Optogenetic control of cell function using engineered photoreceptors. Biol Cell 105:59–72
Pham E, Mills E, Truong K (2011) A synthetic photoactivated protein to generate local or global Ca(2+) signals. Chem Biol 18:880–890
Polstein LR, Gersbach CA (2015) A light-inducible CRISPR-Cas9 system for control of endogenous gene activation. Nat Chem Biol 11:198–200
Prakriya M, Lewis RS (2015) Store-operated calcium channels. Physiol Rev 95:1383–1436
Procopio M, Link J, Engle D, Witczak J, Ritz T, Ahmad M (2016) Kinetic modeling of the Arabidopsis cryptochrome photocycle: FADH(o) accumulation correlates with biological activity. Front Plant Sci 7:888
Pudasaini A, El-Arab KK, Zoltowski BD (2015) LOV-based optogenetic devices: light-driven modules to impart photoregulated control of cellular signaling. Front Mol Biosci 2:18
Putney JW Jr (1986) A model for receptor-regulated calcium entry. Cell Calcium 7:1–12
Quintana A, Rajanikanth V, Farber-Katz S, Gudlur A, Zhang C, Jing J, Zhou Y, Rao A, Hogan PG (2015) TMEM110 regulates the maintenance and remodeling of mammalian ER–plasma membrane junctions competent for STIM–ORAI signaling. Proc Natl Acad Sci U S A 112:E7083–E7092
Rao A (2009) Signaling to gene expression: calcium, calcineurin and NFAT. Nat Immunol 10:3–5
Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Velicelebi G, Stauderman KA (2005) STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol 169:435–445
Sharma S, Quintana A, Findlay GM, Mettlen M, Baust B, Jain M, Nilsson R, Rao A, Hogan PG (2013) An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca2+ entry. Nature 499:238–242
Shen J, Zhao L, Han G (2013) Lanthanide-doped upconverting luminescent nanoparticle platforms for optical imaging-guided drug delivery and therapy. Adv Drug Deliv Rev 65:744–755
Soboloff J, Rothberg BS, Madesh M, Gill DL (2012) STIM proteins: dynamic calcium signal transducers. Nat Rev Mol Cell Biol 13:549–565
Srikanth S, Jung HJ, Kim KD, Souda P, Whitelegge J, Gwack Y (2010) A novel EF-hand protein, CRACR2A, is a cytosolic Ca2+ sensor that stabilizes CRAC channels in T cells. Nat Cell Biol 12:436–446
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
Stathopulos PB, Zheng L, Li GY, Plevin MJ, Ikura M (2008) Structural and mechanistic insights into STIM1-mediated initiation of store-operated calcium entry. Cell 135:110–122
Tan P, He L, Han G, Zhou Y (2016) Optogenetic immunomodulation: shedding light on antitumor immunity. Trends Biotechnol 35(3):215–226
Taslimi A, Vrana JD, Chen D, Borinskaya S, Mayer BJ, Kennedy MJ, Tucker CL (2014) An optimized optogenetic clustering tool for probing protein interaction and function. Nat Commun 5:4925
Taslimi A, Zoltowski B, Miranda JG, Pathak GP, Hughes RM, Tucker CL (2016) Optimized second-generation CRY2-CIB dimerizers and photoactivatable Cre recombinase. Nat Chem Biol 12:425–430
Tischer D, Weiner OD (2014) Illuminating cell signalling with optogenetic tools. Nat Rev Mol Cell Biol 15:551–558
Vig M, Kinet JP (2007) The long and arduous road to CRAC. Cell Calcium 42:157–162
Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, Kraft S, Turner H, Fleig A, Penner R, Kinet JP (2006) CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science 312:1220–1223
Wang H, Vilela M, Winkler A, Tarnawski M, Schlichting I, Yumerefendi H, Kuhlman B, Liu R, Danuser G, Hahn KM (2016) LOVTRAP: an optogenetic system for photoinduced protein dissociation. Nat Methods 13:755–758
Weitzman M, Hahn KM (2014) Optogenetic approaches to cell migration and beyond. Curr Opin Cell Biol 30:112–120
Wu YI, Frey D, Lungu OI, Jaehrig A, Schlichting I, Kuhlman B, Hahn KM (2009) A genetically encoded photoactivatable Rac controls the motility of living cells. Nature 461:104–108
Yuan JP, Zeng W, Dorwart MR, Choi YJ, Worley PF, Muallem S (2009) SOAR and the polybasic STIM1 domains gate and regulate Orai channels. Nat Cell Biol 11:337–343
Zhang K, Cui B (2015) Optogenetic control of intracellular signaling pathways. Trends Biotechnol 33:92–100
Zhang SL, Yu Y, Roos J, Kozak JA, Deerinck TJ, Ellisman MH, Stauderman KA, Cahalan MD (2005) STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature 437:902–905
Zhang Y, Huang L, Li Z, Ma G, Zhou Y, Han G (2016) Illuminating cell signaling with near-infrared light-responsive nanomaterials. ACS Nano 10:3881–3885
Zhou Y, Meraner P, Kwon HT, Machnes D, Oh-hora M, Zimmer J, Huang Y, Stura A, Rao A, Hogan PG (2010) STIM1 gates the store-operated calcium channel ORAI1 in vitro. Nat Struct Mol Biol 17:112–116
Zhou Y, Srinivasan P, Razavi S, Seymour S, Meraner P, Gudlur A, Stathopulos PB, Ikura M, Rao A, Hogan PG (2013) Initial activation of STIM1, the regulator of store-operated calcium entry. Nat Struct Mol Biol 20:973–981
Zimmerman SP, Kuhlman B, Yumerefendi H (2016) Engineering and application of LOV2-based photoswitches. Methods Enzymol 580:169–190
Zoltowski BD, Vaccaro B, Crane BR (2009) Mechanism-based tuning of a LOV domain photoreceptor. Nat Chem Biol 5:827–834
Acknowledgments
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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Ma, G., Wen, S., Huang, Y., Zhou, Y. (2017). The STIM-Orai Pathway: Light-Operated Ca2+ Entry Through Engineered CRAC Channels. In: Groschner, K., Graier, W., Romanin, C. (eds) Store-Operated Ca²⁺ Entry (SOCE) Pathways. Advances in Experimental Medicine and Biology, vol 993. Springer, Cham. https://doi.org/10.1007/978-3-319-57732-6_7
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