Microbial Rhodopsins: Diversity, Mechanisms, and Optogenetic Applications

Overview

Journal Annu Rev Biochem

Publisher Annual Reviews

Specialty Biochemistry

Date 2017 Mar 17

PMID 28301742

Citations 143

Authors

Elena G Govorunova

Oleg A Sineshchekov

Hai Li

John L Spudich

Affiliations

Soon will be listed here.

Abstract

Microbial rhodopsins are a family of photoactive retinylidene proteins widespread throughout the microbial world. They are notable for their diversity of function, using variations of a shared seven-transmembrane helix design and similar photochemical reactions to carry out distinctly different light-driven energy and sensory transduction processes. Their study has contributed to our understanding of how evolution modifies protein scaffolds to create new protein chemistry, and their use as tools to control membrane potential with light is fundamental to optogenetics for research and clinical applications. We review the currently known functions and present more in-depth assessment of three functionally and structurally distinct types discovered over the past two years: (a) anion channelrhodopsins (ACRs) from cryptophyte algae, which enable efficient optogenetic neural suppression; (b) cryptophyte cation channelrhodopsins (CCRs), structurally distinct from the green algae CCRs used extensively for neural activation and from cryptophyte ACRs; and

Citing Articles

Actinorhodopsin: an efficient and robust light-driven proton pump for bionanotechnological applications.

Ayoub N, Djabeur N, Harder D, Jeckelmann J, Ucurum Z, Hirschi S Sci Rep. 2025; 15(1):4054.

PMID: 39900604 PMC: 11790970. DOI: 10.1038/s41598-025-88055-8.

ON-OFF nanopores for optical control of transmembrane ionic communication.

Wang X, Kerckhoffs A, Riexinger J, Cornall M, Langton M, Bayley H Nat Nanotechnol. 2025; .

PMID: 39838209 DOI: 10.1038/s41565-024-01823-x.

Proton reactions: From basic science to biomedical applications.

Bondar A, DeCoursey T Biophys J. 2024; 123(24):E1-E5.

PMID: 39644897 PMC: 11700356. DOI: 10.1016/j.bpj.2024.11.013.

A Detailed View on the (Re)isomerization Dynamics in Microbial Rhodopsins Using Complementary Near-UV and IR Readouts.

Asido M, Lamm G, Lienert J, La Greca M, Kaur J, Mayer A Angew Chem Int Ed Engl. 2024; 64(4):e202416742.

PMID: 39523487 PMC: 11753611. DOI: 10.1002/anie.202416742.

Light-driven anion-pumping rhodopsin with unique cytoplasmic anion-release mechanism.

Ishizuka T, Suzuki K, Konno M, Shibata K, Kawasaki Y, Akiyama H J Biol Chem. 2024; 300(10):107797.

PMID: 39305959 PMC: 11532467. DOI: 10.1016/j.jbc.2024.107797.

References

Inoue K, Kato Y, Kandori H . Light-driven ion-translocating rhodopsins in marine bacteria. Trends Microbiol. 2014; 23(2):91-8. DOI: 10.1016/j.tim.2014.10.009. View

Zhao M, Alleva R, Ma H, Daniel A, Schwartz T . Optogenetic tools for modulating and probing the epileptic network. Epilepsy Res. 2015; 116:15-26. PMC: 4567692. DOI: 10.1016/j.eplepsyres.2015.06.010. View

Lorenz-Fonfria V, Bamann C, Resler T, Schlesinger R, Bamberg E, Heberle J . Temporal evolution of helix hydration in a light-gated ion channel correlates with ion conductance. Proc Natl Acad Sci U S A. 2015; 112(43):E5796-804. PMC: 4629336. DOI: 10.1073/pnas.1511462112. View

Berndt A, Lee S, Wietek J, Ramakrishnan C, Steinberg E, Rashid A . Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity. Proc Natl Acad Sci U S A. 2015; 113(4):822-9. PMC: 4743797. DOI: 10.1073/pnas.1523341113. View

Radu I, Bamann C, Nack M, Nagel G, Bamberg E, Heberle J . Conformational changes of channelrhodopsin-2. J Am Chem Soc. 2009; 131(21):7313-9. DOI: 10.1021/ja8084274. View

Cohen A . Optogenetics: Turning the Microscope on Its Head. Biophys J. 2016; 110(5):997-1003. PMC: 4788753. DOI: 10.1016/j.bpj.2016.02.011. View

Gushchin I, Shevchenko V, Polovinkin V, Kovalev K, Alekseev A, Round E . Crystal structure of a light-driven sodium pump. Nat Struct Mol Biol. 2015; 22(5):390-5. DOI: 10.1038/nsmb.3002. View

Inoue K, Ono H, Abe-Yoshizumi R, Yoshizawa S, Ito H, Kogure K . A light-driven sodium ion pump in marine bacteria. Nat Commun. 2013; 4:1678. DOI: 10.1038/ncomms2689. View

Gao S, Nagpal J, Schneider M, Kozjak-Pavlovic V, Nagel G, Gottschalk A . Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp. Nat Commun. 2015; 6:8046. PMC: 4569695. DOI: 10.1038/ncomms9046. View

10.

Schmies G, Luttenberg B, Chizhov I, Engelhard M, Becker A, Bamberg E . Sensory rhodopsin II from the haloalkaliphilic natronobacterium pharaonis: light-activated proton transfer reactions. Biophys J. 2000; 78(2):967-76. PMC: 1300699. DOI: 10.1016/S0006-3495(00)76654-9. View

11.

Verhoefen M, Bamann C, Blocher R, Forster U, Bamberg E, Wachtveitl J . The photocycle of channelrhodopsin-2: ultrafast reaction dynamics and subsequent reaction steps. Chemphyschem. 2010; 11(14):3113-22. DOI: 10.1002/cphc.201000181. View

12.

Ritter E, Stehfest K, Berndt A, Hegemann P, Bartl F . Monitoring light-induced structural changes of Channelrhodopsin-2 by UV-visible and Fourier transform infrared spectroscopy. J Biol Chem. 2008; 283(50):35033-41. PMC: 3259888. DOI: 10.1074/jbc.M806353200. View

13.

Venter J, Remington K, Heidelberg J, Halpern A, Rusch D, Eisen J . Environmental genome shotgun sequencing of the Sargasso Sea. Science. 2004; 304(5667):66-74. DOI: 10.1126/science.1093857. View

14.

Jung K, Trivedi V, Spudich J . Demonstration of a sensory rhodopsin in eubacteria. Mol Microbiol. 2003; 47(6):1513-22. DOI: 10.1046/j.1365-2958.2003.03395.x. View

15.

Grubb M, Burrone J . Channelrhodopsin-2 localised to the axon initial segment. PLoS One. 2010; 5(10):e13761. PMC: 2966437. DOI: 10.1371/journal.pone.0013761. View

16.

Berndt A, Lee S, Ramakrishnan C, Deisseroth K . Structure-guided transformation of channelrhodopsin into a light-activated chloride channel. Science. 2014; 344(6182):420-4. PMC: 4096039. DOI: 10.1126/science.1252367. View

17.

Spudich E, Spudich J . Control of transmembrane ion fluxes to select halorhodopsin-deficient and other energy-transduction mutants of Halobacterium halobium. Proc Natl Acad Sci U S A. 1982; 79(14):4308-12. PMC: 346660. DOI: 10.1073/pnas.79.14.4308. View

18.

Govorunova E, Sineshchekov O, Janz R, Liu X, Spudich J . NEUROSCIENCE. Natural light-gated anion channels: A family of microbial rhodopsins for advanced optogenetics. Science. 2015; 349(6248):647-50. PMC: 4764398. DOI: 10.1126/science.aaa7484. View

19.

Nagel G, Szellas T, Huhn W, Kateriya S, Adeishvili N, Berthold P . Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci U S A. 2003; 100(24):13940-5. PMC: 283525. DOI: 10.1073/pnas.1936192100. View

20.

Sineshchekov O, Sasaki J, Wang J, Spudich J . Attractant and repellent signaling conformers of sensory rhodopsin-transducer complexes. Biochemistry. 2010; 49(31):6696-704. PMC: 2914491. DOI: 10.1021/bi100798w. View