Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools

N. Azimihashemi; K. Erbguth; A. Vogt; T. Riemensperger; E. Rauch; D. Woodmansee; J. Nagpal; M. Brauner; M. Sheves; A. Fiala; L. Kattner; D. Trauner; P. Hegemann; A. Gottschalk; J. F. Liewald

doi:10.1038/ncomms6810

Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools

N. Azimihashemi, K. Erbguth, A. Vogt, T. Riemensperger, E. Rauch, D. Woodmansee, J. Nagpal, M. Brauner, M. Sheves, A. Fiala, L. Kattner, D. Trauner, P. Hegemann, A. Gottschalk, J. F. Liewald

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Optogenetic tools have become indispensable in neuroscience to stimulate or inhibit excitable cells by light. Channelrhodopsin-2 (ChR2) variants have been established by mutating the opsin backbone or by mining related algal genomes. As an alternative strategy, we surveyed synthetic retinal analogues combined with microbial rhodopsins for functional and spectral properties, capitalizing on assays in C. elegans, HEK cells and larval Drosophila. Compared with all-trans retinal (ATR), Dimethylamino-retinal (DMAR) shifts the action spectra maxima of ChR2 variants H134R and H134R/T159C from 480 to 520 nm. Moreover, DMAR decelerates the photocycle of ChR2(H134R) and (H134R/T159C), thereby reducing the light intensity required for persistent channel activation. In hyperpolarizing archaerhodopsin-3 and Mac, naphthyl-retinal and thiophene-retinal support activity alike ATR, yet at altered peak wavelengths. Our experiments enable applications of retinal analogues in colour tuning and altering photocycle characteristics of optogenetic tools, thereby increasing the operational light sensitivity of existing cell lines or transgenic animals.

Original language	English (US)
Article number	5810
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6810
State	Published - 2014

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms6810

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Azimihashemi, N., Erbguth, K., Vogt, A., Riemensperger, T., Rauch, E., Woodmansee, D., Nagpal, J., Brauner, M., Sheves, M., Fiala, A., Kattner, L., Trauner, D., Hegemann, P., Gottschalk, A., & Liewald, J. F. (2014). Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools. Nature communications, 5, Article 5810. https://doi.org/10.1038/ncomms6810

Azimihashemi, N, Erbguth, K, Vogt, A, Riemensperger, T, Rauch, E, Woodmansee, D, Nagpal, J, Brauner, M, Sheves, M, Fiala, A, Kattner, L, Trauner, D, Hegemann, P, Gottschalk, A & Liewald, JF 2014, 'Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools', Nature communications, vol. 5, 5810. https://doi.org/10.1038/ncomms6810

@article{0072760f8bec45e0a01b8bc82af25b57,

title = "Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools",

abstract = "Optogenetic tools have become indispensable in neuroscience to stimulate or inhibit excitable cells by light. Channelrhodopsin-2 (ChR2) variants have been established by mutating the opsin backbone or by mining related algal genomes. As an alternative strategy, we surveyed synthetic retinal analogues combined with microbial rhodopsins for functional and spectral properties, capitalizing on assays in C. elegans, HEK cells and larval Drosophila. Compared with all-trans retinal (ATR), Dimethylamino-retinal (DMAR) shifts the action spectra maxima of ChR2 variants H134R and H134R/T159C from 480 to 520 nm. Moreover, DMAR decelerates the photocycle of ChR2(H134R) and (H134R/T159C), thereby reducing the light intensity required for persistent channel activation. In hyperpolarizing archaerhodopsin-3 and Mac, naphthyl-retinal and thiophene-retinal support activity alike ATR, yet at altered peak wavelengths. Our experiments enable applications of retinal analogues in colour tuning and altering photocycle characteristics of optogenetic tools, thereby increasing the operational light sensitivity of existing cell lines or transgenic animals.",

author = "N. Azimihashemi and K. Erbguth and A. Vogt and T. Riemensperger and E. Rauch and D. Woodmansee and J. Nagpal and M. Brauner and M. Sheves and A. Fiala and L. Kattner and D. Trauner and P. Hegemann and A. Gottschalk and Liewald, {J. F.}",

note = "Funding Information: We thank Elisabeth Fischer, Kenan Bozh{\"u}y{\"u}k and Professor Helge B. Bode for assistance. The research was supported by the European Community{\textquoteright}s Seventh Framework Programme FP7/2007–2013 (EUTrigTreat; grant agreement HEALTH-F2-2009-241526, to A.G. and L.K.) and the Deutsche Forschungsgemeinschaft (DFG; grants GO1011/3-1, GO1011/4-1, SFB807, Cluster of Excellence Frankfurt, Macromolecular Complexes (EXC115), FOR1279 all to A.G.); FOR1279 P8 and SFB1078 B2 (to P.H.); SFB 889/B04 and C02 (to A.F. and T.R.). A.V. was supported by the Leibniz Graduate School of Molecular Biophysics. Publisher Copyright: {\textcopyright} 2014 Macmillan Publishers Limited. All rights reserved.",

year = "2014",

doi = "10.1038/ncomms6810",

language = "English (US)",

volume = "5",

journal = "Nature communications",

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T1 - Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools

AU - Azimihashemi, N.

AU - Erbguth, K.

AU - Vogt, A.

AU - Riemensperger, T.

AU - Rauch, E.

AU - Woodmansee, D.

AU - Nagpal, J.

AU - Brauner, M.

AU - Sheves, M.

AU - Fiala, A.

AU - Kattner, L.

AU - Trauner, D.

AU - Hegemann, P.

AU - Gottschalk, A.

AU - Liewald, J. F.

N1 - Funding Information: We thank Elisabeth Fischer, Kenan Bozhüyük and Professor Helge B. Bode for assistance. The research was supported by the European Community’s Seventh Framework Programme FP7/2007–2013 (EUTrigTreat; grant agreement HEALTH-F2-2009-241526, to A.G. and L.K.) and the Deutsche Forschungsgemeinschaft (DFG; grants GO1011/3-1, GO1011/4-1, SFB807, Cluster of Excellence Frankfurt, Macromolecular Complexes (EXC115), FOR1279 all to A.G.); FOR1279 P8 and SFB1078 B2 (to P.H.); SFB 889/B04 and C02 (to A.F. and T.R.). A.V. was supported by the Leibniz Graduate School of Molecular Biophysics. Publisher Copyright: © 2014 Macmillan Publishers Limited. All rights reserved.

PY - 2014

Y1 - 2014

N2 - Optogenetic tools have become indispensable in neuroscience to stimulate or inhibit excitable cells by light. Channelrhodopsin-2 (ChR2) variants have been established by mutating the opsin backbone or by mining related algal genomes. As an alternative strategy, we surveyed synthetic retinal analogues combined with microbial rhodopsins for functional and spectral properties, capitalizing on assays in C. elegans, HEK cells and larval Drosophila. Compared with all-trans retinal (ATR), Dimethylamino-retinal (DMAR) shifts the action spectra maxima of ChR2 variants H134R and H134R/T159C from 480 to 520 nm. Moreover, DMAR decelerates the photocycle of ChR2(H134R) and (H134R/T159C), thereby reducing the light intensity required for persistent channel activation. In hyperpolarizing archaerhodopsin-3 and Mac, naphthyl-retinal and thiophene-retinal support activity alike ATR, yet at altered peak wavelengths. Our experiments enable applications of retinal analogues in colour tuning and altering photocycle characteristics of optogenetic tools, thereby increasing the operational light sensitivity of existing cell lines or transgenic animals.

AB - Optogenetic tools have become indispensable in neuroscience to stimulate or inhibit excitable cells by light. Channelrhodopsin-2 (ChR2) variants have been established by mutating the opsin backbone or by mining related algal genomes. As an alternative strategy, we surveyed synthetic retinal analogues combined with microbial rhodopsins for functional and spectral properties, capitalizing on assays in C. elegans, HEK cells and larval Drosophila. Compared with all-trans retinal (ATR), Dimethylamino-retinal (DMAR) shifts the action spectra maxima of ChR2 variants H134R and H134R/T159C from 480 to 520 nm. Moreover, DMAR decelerates the photocycle of ChR2(H134R) and (H134R/T159C), thereby reducing the light intensity required for persistent channel activation. In hyperpolarizing archaerhodopsin-3 and Mac, naphthyl-retinal and thiophene-retinal support activity alike ATR, yet at altered peak wavelengths. Our experiments enable applications of retinal analogues in colour tuning and altering photocycle characteristics of optogenetic tools, thereby increasing the operational light sensitivity of existing cell lines or transgenic animals.

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Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools

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