NEUROSCIENCE. Natural Light-gated Anion Channels: A Family of Microbial Rhodopsins for Advanced Optogenetics

Overview

Journal Science

Specialty Science

Date 2015 Jun 27

PMID 26113638

Citations 294

Authors

Elena G Govorunova

Oleg A Sineshchekov

Roger Janz

Xiaoqin Liu

John L Spudich

Affiliations

Soon will be listed here.

Abstract

Light-gated rhodopsin cation channels from chlorophyte algae have transformed neuroscience research through their use as membrane-depolarizing optogenetic tools for targeted photoactivation of neuron firing. Photosuppression of neuronal action potentials has been limited by the lack of equally efficient tools for membrane hyperpolarization. We describe anion channel rhodopsins (ACRs), a family of light-gated anion channels from cryptophyte algae that provide highly sensitive and efficient membrane hyperpolarization and neuronal silencing through light-gated chloride conduction. ACRs strictly conducted anions, completely excluding protons and larger cations, and hyperpolarized the membrane of cultured animal cells with much faster kinetics at less than one-thousandth of the light intensity required by the most efficient currently available optogenetic proteins. Natural ACRs provide optogenetic inhibition tools with unprecedented light sensitivity and temporal precision.

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References

Zhang F, Wang L, Brauner M, Liewald J, Kay K, Watzke N . Multimodal fast optical interrogation of neural circuitry. Nature. 2007; 446(7136):633-9. DOI: 10.1038/nature05744. View

Deisseroth K . Optogenetics. Nat Methods. 2010; 8(1):26-9. PMC: 6814250. DOI: 10.1038/nmeth.f.324. View

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

Sineshchekov O, Govorunova E, Jung K, Zauner S, Maier U, Spudich J . Rhodopsin-mediated photoreception in cryptophyte flagellates. Biophys J. 2005; 89(6):4310-9. PMC: 1366995. DOI: 10.1529/biophysj.105.070920. View

Lin J, Knutsen P, Muller A, Kleinfeld D, Tsien R . ReaChR: a red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation. Nat Neurosci. 2013; 16(10):1499-508. PMC: 3793847. DOI: 10.1038/nn.3502. View

Spudich J, Sineshchekov O, Govorunova E . Mechanism divergence in microbial rhodopsins. Biochim Biophys Acta. 2013; 1837(5):546-52. PMC: 3844102. DOI: 10.1016/j.bbabio.2013.06.006. View

Wietek J, Wiegert J, Adeishvili N, Schneider F, Watanabe H, Tsunoda S . Conversion of channelrhodopsin into a light-gated chloride channel. Science. 2014; 344(6182):409-12. DOI: 10.1126/science.1249375. View

Bregestovski P, Waseem T, Mukhtarov M . Genetically encoded optical sensors for monitoring of intracellular chloride and chloride-selective channel activity. Front Mol Neurosci. 2010; 2:15. PMC: 2802328. DOI: 10.3389/neuro.02.015.2009. View

Ernst O, Lodowski D, Elstner M, Hegemann P, Brown L, Kandori H . Microbial and animal rhodopsins: structures, functions, and molecular mechanisms. Chem Rev. 2013; 114(1):126-63. PMC: 3979449. DOI: 10.1021/cr4003769. View

10.

Jentsch T, Stein V, Weinreich F, Zdebik A . Molecular structure and physiological function of chloride channels. Physiol Rev. 2002; 82(2):503-68. DOI: 10.1152/physrev.00029.2001. View

11.

Govorunova E, Sineshchekov O, Li H, Janz R, Spudich J . Characterization of a highly efficient blue-shifted channelrhodopsin from the marine alga Platymonas subcordiformis. J Biol Chem. 2013; 288(41):29911-22. PMC: 3795289. DOI: 10.1074/jbc.M113.505495. View

12.

Gradinaru V, Thompson K, Deisseroth K . eNpHR: a Natronomonas halorhodopsin enhanced for optogenetic applications. Brain Cell Biol. 2008; 36(1-4):129-39. PMC: 2588488. DOI: 10.1007/s11068-008-9027-6. View

13.

Han X, Boyden E . Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. PLoS One. 2007; 2(3):e299. PMC: 1808431. DOI: 10.1371/journal.pone.0000299. View

14.

Sineshchekov O, Jung K, Spudich J . Two rhodopsins mediate phototaxis to low- and high-intensity light in Chlamydomonas reinhardtii. Proc Natl Acad Sci U S A. 2002; 99(13):8689-94. PMC: 124360. DOI: 10.1073/pnas.122243399. View

15.

Chow B, Boyden E . Optogenetics and translational medicine. Sci Transl Med. 2013; 5(177):177ps5. DOI: 10.1126/scitranslmed.3003101. View

16.

Curtis B, Tanifuji G, Burki F, Gruber A, Irimia M, Maruyama S . Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs. Nature. 2012; 492(7427):59-65. DOI: 10.1038/nature11681. View

17.

Feldbauer K, Zimmermann D, Pintschovius V, Spitz J, Bamann C, Bamberg E . Channelrhodopsin-2 is a leaky proton pump. Proc Natl Acad Sci U S A. 2009; 106(30):12317-22. PMC: 2718366. DOI: 10.1073/pnas.0905852106. View

18.

Gradinaru V, Zhang F, Ramakrishnan C, Mattis J, Prakash R, Diester I . Molecular and cellular approaches for diversifying and extending optogenetics. Cell. 2010; 141(1):154-165. PMC: 4160532. DOI: 10.1016/j.cell.2010.02.037. View

19.

Klapoetke N, Murata Y, Kim S, Pulver S, Birdsey-Benson A, Cho Y . Independent optical excitation of distinct neural populations. Nat Methods. 2014; 11(3):338-46. PMC: 3943671. DOI: 10.1038/nmeth.2836. View

20.

Chuong A, Miri M, Busskamp V, Matthews G, Acker L, Sorensen A . Noninvasive optical inhibition with a red-shifted microbial rhodopsin. Nat Neurosci. 2014; 17(8):1123-9. PMC: 4184214. DOI: 10.1038/nn.3752. View