Universität zu Köln

Govorunova, Elena G., Sineshchekov, Oleg A., Rodarte, Elsa M. ORCID: 0000-0001-7138-0790, Janz, Roger ORCID: 0000-0002-9872-0596, Morelle, Olivier, Melkonian, Michael, Wong, Gane K. -S. and Spudich, John L. (2017). The Expanding Family of Natural Anion Channelrhodopsins Reveals Large Variations in Kinetics, Conductance, and Spectral Sensitivity. Sci Rep, 7. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Natural anion channelrhodopsins (ACRs) discovered in the cryptophyte alga Guillardia theta generate large hyperpolarizing currents at membrane potentials above the Nernst equilibrium potential for Cland thus can be used as efficient inhibitory tools for optogenetics. We have identified and characterized new ACR homologs in different cryptophyte species, showing that all of them are anion-selective, and thus expanded this protein family to 20 functionally confirmed members. Sequence comparison of natural ACRs and engineered Cl--conducting mutants of cation channelrhodopsins (CCRs) showed radical differences in their anion selectivity filters. In particular, the Glu90 residue in channelrhodopsin 2, which needed to be mutated to a neutral or alkaline residue to confer anion selectivity to CCRs, is nevertheless conserved in all of the ACRs identified. The new ACRs showed a large variation of the amplitude, kinetics, and spectral sensitivity of their photocurrents. A notable variant, designated ZipACR, is particularly promising for inhibitory optogenetics because of its combination of larger current amplitudes than those of previously reported ACRs and an unprecedentedly fast conductance cycle (current half-decay time 2-4 ms depending on voltage). ZipACR expressed in cultured mouse hippocampal neurons enabled precise photoinhibition of individual spikes in trains of up to 50 Hz frequency.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Govorunova, Elena G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sineshchekov, Oleg A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rodarte, Elsa M. UNSPECIFIED orcid.org/0000-0001-7138-0790 UNSPECIFIED Janz, Roger UNSPECIFIED orcid.org/0000-0002-9872-0596 UNSPECIFIED Morelle, Olivier UNSPECIFIED UNSPECIFIED UNSPECIFIED Melkonian, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Wong, Gane K. -S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Spudich, John L. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-236808
DOI:	10.1038/srep43358
Journal or Publication Title:	Sci Rep
Volume:	7
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEOMONAS-SULCATA; SEQUENCE ALIGNMENT; CHLORIDE CHANNEL; LIGHT; OPTOGENETICS; PERFORMANCE; PHOTOCYCLE; RHODOPSINS; MODELS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23680