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Nat Commun. 2019 Jul 25;10(1):3315. doi: 10.1038/s41467-019-11322-6.

MerMAIDs: a family of metagenomically discovered marine anion-conducting and intensely desensitizing channelrhodopsins.

Author information

1
Institute for Biology, Experimental Biophysics, Humboldt-Universität zu Berlin, Invalidenstraße 42, 10115, Berlin, Germany.
2
Research Group Synaptic Wiring and Information Processing, Center for Molecular Neurobiology Hamburg, Falkenried 94, 20251, Hamburg, Germany.
3
Technion-Israel Institute of Technology, 32000, Haifa, Israel.
4
Department of Plant Microbe Interactions, Max Planck Institute for Plant Breeding Research, Cologne, 50829, Germany.
5
Institute for Chemistry, Physical Chemistry/Biophysical Chemistry, Technische Universität Berlin, Straße des 17. Juni 135, 10623, Berlin, Germany.
6
Institute for Biology, Biophysical Chemistry, Humboldt-Universität zu Berlin, Invalidenstraße 42, 10115, Berlin, Germany.
7
Institute for Biology, Experimental Biophysics, Humboldt-Universität zu Berlin, Invalidenstraße 42, 10115, Berlin, Germany. hegemann@rz.hu-berlin.de.
8
Institute for Biology, Experimental Biophysics, Humboldt-Universität zu Berlin, Invalidenstraße 42, 10115, Berlin, Germany. jonaswietek@gmail.com.
9
Department of Neurobiology, Weizmann Institute of Science, 7610001, Rehovot, Israel. jonaswietek@gmail.com.

Abstract

Channelrhodopsins (ChRs) are algal light-gated ion channels widely used as optogenetic tools for manipulating neuronal activity. ChRs desensitize under continuous bright-light illumination, resulting in a significant decline of photocurrents. Here we describe a metagenomically identified family of phylogenetically distinct anion-conducting ChRs (designated MerMAIDs). MerMAIDs almost completely desensitize during continuous illumination due to accumulation of a late non-conducting photointermediate that disrupts the ion permeation pathway. MerMAID desensitization can be fully explained by a single photocycle in which a long-lived desensitized state follows the short-lived conducting state. A conserved cysteine is the critical factor in desensitization, as its mutation results in recovery of large stationary photocurrents. The rapid desensitization of MerMAIDs enables their use as optogenetic silencers for transient suppression of individual action potentials without affecting subsequent spiking during continuous illumination. Our results could facilitate the development of optogenetic tools from metagenomic databases and enhance general understanding of ChR function.

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