Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling
Rodrigo G. Fernandez Lahore (),
Niccolò P. Pampaloni,
Enrico Schiewer,
M.-Marcel Heim,
Linda Tillert,
Johannes Vierock,
Johannes Oppermann,
Jakob Walther,
Dietmar Schmitz,
David Owald,
Andrew J. R. Plested,
Benjamin R. Rost and
Peter Hegemann
Additional contact information
Rodrigo G. Fernandez Lahore: Humboldt-Universität zu Berlin
Niccolò P. Pampaloni: Leibniz-Institut für Molekulare Pharmakologie
Enrico Schiewer: Humboldt-Universität zu Berlin
M.-Marcel Heim: Charité – Universitätsmedizin Berlin
Linda Tillert: Humboldt-Universität zu Berlin
Johannes Vierock: Humboldt-Universität zu Berlin
Johannes Oppermann: Humboldt-Universität zu Berlin
Jakob Walther: Charité – Universitätsmedizin Berlin
Dietmar Schmitz: Charité – Universitätsmedizin Berlin
David Owald: Charité – Universitätsmedizin Berlin
Andrew J. R. Plested: Leibniz-Institut für Molekulare Pharmakologie
Benjamin R. Rost: German Center for Neurodegenerative Diseases (DZNE)
Peter Hegemann: Humboldt-Universität zu Berlin
Nature Communications, 2022, vol. 13, issue 1, 1-18
Abstract:
Abstract Channelrhodopsins are light-gated ion channels used to control excitability of designated cells in large networks with high spatiotemporal resolution. While ChRs selective for H+, Na+, K+ and anions have been discovered or engineered, Ca2+-selective ChRs have not been reported to date. Here, we analyse ChRs and mutant derivatives with regard to their Ca2+ permeability and improve their Ca2+ affinity by targeted mutagenesis at the central selectivity filter. The engineered channels, termed CapChR1 and CapChR2 for calcium-permeable channelrhodopsins, exhibit reduced sodium and proton conductance in connection with strongly improved Ca2+ permeation at negative voltage and low extracellular Ca2+ concentrations. In cultured cells and neurons, CapChR2 reliably increases intracellular Ca2+ concentrations. Moreover, CapChR2 can robustly trigger Ca2+ signalling in hippocampal neurons. When expressed together with genetically encoded Ca2+ indicators in Drosophila melanogaster mushroom body output neurons, CapChRs mediate light-evoked Ca2+ entry in brain explants.
Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35373-4
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DOI: 10.1038/s41467-022-35373-4
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