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MerMAIDs: a family of metagenomically discovered marine anion-conducting and intensely desensitizing channelrhodopsins
Citation key Oppermann2019
Author Oppermann, Johannes and Fischer, Paul and Silapetere, Arita and Liepe, Bernhard and Rodriguez-Rozada, Silvia and Flores-Uribe, José and Peter, Enrico and Keidel, Anke and Vierock, Johannes and Kaufmann, Joel and Broser, Matthias and Luck, Meike and Bartl, Franz and Hildebrandt, Peter and Wiegert, J. Simon and Béjà, Oded and Hegemann, Peter and Wietek, Jonas
Pages 3315
Year 2019
ISSN 2041-1723
Journal Nature Communications
Volume 10
Number 1
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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