Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2017 Mar 21

PMID 28319307

Citations 43

Authors

Stephanie Kainrath

Manuela Stadler

Eva Reichhart

Martin Distel

Harald Janovjak

Affiliations

Soon will be listed here.

Abstract

Optogenetics and photopharmacology provide spatiotemporally precise control over protein interactions and protein function in cells and animals. Optogenetic methods that are sensitive to green light and can be used to break protein complexes are not broadly available but would enable multichromatic experiments with previously inaccessible biological targets. Herein, we repurposed cobalamin (vitamin B12) binding domains of bacterial CarH transcription factors for green-light-induced receptor dissociation. In cultured cells, we observed oligomerization-induced cell signaling for the fibroblast growth factor receptor 1 fused to cobalamin-binding domains in the dark that was rapidly eliminated upon illumination. In zebrafish embryos expressing fusion receptors, green light endowed control over aberrant fibroblast growth factor signaling during development. Green-light-induced domain dissociation and light-inactivated receptors will critically expand the optogenetic toolbox for control of biological processes.

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References

Jost M, Simpson J, Drennan C . The Transcription Factor CarH Safeguards Use of Adenosylcobalamin as a Light Sensor by Altering the Photolysis Products. Biochemistry. 2015; 54(21):3231-4. PMC: 4455981. DOI: 10.1021/acs.biochem.5b00416. View

Diez A, Ortiz-Guerrero J, Ortega A, Elias-Arnanz M, Padmanabhan S, Garcia de la Torre J . Analytical ultracentrifugation studies of oligomerization and DNA-binding of TtCarH, a Thermus thermophilus coenzyme B12-based photosensory regulator. Eur Biophys J. 2013; 42(6):463-76. DOI: 10.1007/s00249-013-0897-x. View

Bugaj L, Choksi A, Mesuda C, Kane R, Schaffer D . Optogenetic protein clustering and signaling activation in mammalian cells. Nat Methods. 2013; 10(3):249-52. DOI: 10.1038/nmeth.2360. View

Carmel R . Current concepts in cobalamin deficiency. Annu Rev Med. 2000; 51:357-75. DOI: 10.1146/annurev.med.51.1.357. View

Schlessinger J . Cell signaling by receptor tyrosine kinases. Cell. 2000; 103(2):211-25. DOI: 10.1016/s0092-8674(00)00114-8. View

Banerjee R . B12 trafficking in mammals: A for coenzyme escort service. ACS Chem Biol. 2006; 1(3):149-59. DOI: 10.1021/cb6001174. View

Kholodenko B . Negative feedback and ultrasensitivity can bring about oscillations in the mitogen-activated protein kinase cascades. Eur J Biochem. 2000; 267(6):1583-8. DOI: 10.1046/j.1432-1327.2000.01197.x. View

Conrad K, Bilwes A, Crane B . Light-induced subunit dissociation by a light-oxygen-voltage domain photoreceptor from Rhodobacter sphaeroides. Biochemistry. 2012; 52(2):378-91. PMC: 3582384. DOI: 10.1021/bi3015373. View

Wang X, Chen X, Yang Y . Spatiotemporal control of gene expression by a light-switchable transgene system. Nat Methods. 2012; 9(3):266-9. DOI: 10.1038/nmeth.1892. View

10.

Turner N, Grose R . Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010; 10(2):116-29. DOI: 10.1038/nrc2780. View

11.

Reichhart E, Ingles-Prieto A, Tichy A, McKenzie C, Janovjak H . A Phytochrome Sensory Domain Permits Receptor Activation by Red Light. Angew Chem Int Ed Engl. 2016; 55(21):6339-42. DOI: 10.1002/anie.201601736. View

12.

Wang H, Vilela M, Winkler A, Tarnawski M, Schlichting I, Yumerefendi H . LOVTRAP: an optogenetic system for photoinduced protein dissociation. Nat Methods. 2016; 13(9):755-8. PMC: 5137947. DOI: 10.1038/nmeth.3926. View

13.

Shankaran H, Ippolito D, Chrisler W, Resat H, Bollinger N, Opresko L . Rapid and sustained nuclear-cytoplasmic ERK oscillations induced by epidermal growth factor. Mol Syst Biol. 2009; 5:332. PMC: 2824491. DOI: 10.1038/msb.2009.90. View

14.

Kainrath S, Stadler M, Reichhart E, Distel M, Janovjak H . Green-Light-Induced Inactivation of Receptor Signaling Using Cobalamin-Binding Domains. Angew Chem Int Ed Engl. 2017; 56(16):4608-4611. PMC: 5396336. DOI: 10.1002/anie.201611998. View

15.

Takano H, Obitsu S, Beppu T, Ueda K . Light-induced carotenogenesis in Streptomyces coelicolor A3(2): identification of an extracytoplasmic function sigma factor that directs photodependent transcription of the carotenoid biosynthesis gene cluster. J Bacteriol. 2005; 187(5):1825-32. PMC: 1064024. DOI: 10.1128/JB.187.5.1825-1832.2005. View

16.

Zittoun J, Zittoun R . Modern clinical testing strategies in cobalamin and folate deficiency. Semin Hematol. 1999; 36(1):35-46. View

17.

Levskaya A, Weiner O, Lim W, Voigt C . Spatiotemporal control of cell signalling using a light-switchable protein interaction. Nature. 2009; 461(7266):997-1001. PMC: 2989900. DOI: 10.1038/nature08446. View

18.

Jost M, Fernandez-Zapata J, Polanco M, Ortiz-Guerrero J, Chen P, Kang G . Structural basis for gene regulation by a B12-dependent photoreceptor. Nature. 2015; 526(7574):536-41. PMC: 4634937. DOI: 10.1038/nature14950. View

19.

Ota S, Tonou-Fujimori N, Yamasu K . The roles of the FGF signal in zebrafish embryos analyzed using constitutive activation and dominant-negative suppression of different FGF receptors. Mech Dev. 2008; 126(1-2):1-17. DOI: 10.1016/j.mod.2008.10.008. View

20.

Ortiz-Guerrero J, Polanco M, Murillo F, Padmanabhan S, Elias-Arnanz M . Light-dependent gene regulation by a coenzyme B12-based photoreceptor. Proc Natl Acad Sci U S A. 2011; 108(18):7565-70. PMC: 3088613. DOI: 10.1073/pnas.1018972108. View