A second photoactivatable state of the anion-conducting channelrhodopsin GtACR1 empowers persistent activity
Abstract Optogenetics is a method to regulate cells, tissues and organisms using light. It is applied to study neurons and to develop diagnostic and therapeutic tools for neuron-related diseases. The cation-conducting channelrhodopsin ChR2 triggers photoinduced depolarization of neuronal cells but g...
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Nature Portfolio
2025-08-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08560-4 |
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| author | Kristin Labudda Mohamad Javad Norahan Lisa-Marie Hübner Philipp Althoff Klaus Gerwert Mathias Lübben Till Rudack Carsten Kötting |
| author_facet | Kristin Labudda Mohamad Javad Norahan Lisa-Marie Hübner Philipp Althoff Klaus Gerwert Mathias Lübben Till Rudack Carsten Kötting |
| author_sort | Kristin Labudda |
| collection | DOAJ |
| description | Abstract Optogenetics is a method to regulate cells, tissues and organisms using light. It is applied to study neurons and to develop diagnostic and therapeutic tools for neuron-related diseases. The cation-conducting channelrhodopsin ChR2 triggers photoinduced depolarization of neuronal cells but generates lower ion currents due to the syn-pathway of its branched photocycle. In contrast, the homologous anion-conducting ACR1 from Guillardia theta (GtACR1), exhibits high photocurrents. Here, we investigate the mechanistic cause for the observed high photocurrents in GtACR1 using FTIR spectroscopy. Unexpectedly, we discovered that the O intermediate of GtACR1 is photoactivable, allowing for fast and efficient channel reopening. Our vibrational spectra show a photocyclic reaction sequence after O excitation similar to the ground state photocycle but with slightly altered channel conformation and protonation states. Our results provide deeper insights into the gating mechanism of channelrhodopsins and pave the way to advance the development of optimized optogenetic tools in future. |
| format | Article |
| id | doaj-art-aa88609e5e594a75b5ccb0a69cc19e86 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-aa88609e5e594a75b5ccb0a69cc19e862025-08-20T03:46:21ZengNature PortfolioCommunications Biology2399-36422025-08-018111210.1038/s42003-025-08560-4A second photoactivatable state of the anion-conducting channelrhodopsin GtACR1 empowers persistent activityKristin Labudda0Mohamad Javad Norahan1Lisa-Marie Hübner2Philipp Althoff3Klaus Gerwert4Mathias Lübben5Till Rudack6Carsten Kötting7Center for Protein Diagnostics (PRODI), Biospectroscopy, Ruhr University BochumCenter for Protein Diagnostics (PRODI), Biospectroscopy, Ruhr University BochumCenter for Protein Diagnostics (PRODI), Biospectroscopy, Ruhr University BochumCenter for Protein Diagnostics (PRODI), Biospectroscopy, Ruhr University BochumCenter for Protein Diagnostics (PRODI), Biospectroscopy, Ruhr University BochumCenter for Protein Diagnostics (PRODI), Biospectroscopy, Ruhr University BochumStructural Bioinformatics Group, Regensburg Center for Biochemistry, Regensburg Center for Ultrafast Nanoscopy, University of RegensburgCenter for Protein Diagnostics (PRODI), Biospectroscopy, Ruhr University BochumAbstract Optogenetics is a method to regulate cells, tissues and organisms using light. It is applied to study neurons and to develop diagnostic and therapeutic tools for neuron-related diseases. The cation-conducting channelrhodopsin ChR2 triggers photoinduced depolarization of neuronal cells but generates lower ion currents due to the syn-pathway of its branched photocycle. In contrast, the homologous anion-conducting ACR1 from Guillardia theta (GtACR1), exhibits high photocurrents. Here, we investigate the mechanistic cause for the observed high photocurrents in GtACR1 using FTIR spectroscopy. Unexpectedly, we discovered that the O intermediate of GtACR1 is photoactivable, allowing for fast and efficient channel reopening. Our vibrational spectra show a photocyclic reaction sequence after O excitation similar to the ground state photocycle but with slightly altered channel conformation and protonation states. Our results provide deeper insights into the gating mechanism of channelrhodopsins and pave the way to advance the development of optimized optogenetic tools in future.https://doi.org/10.1038/s42003-025-08560-4 |
| spellingShingle | Kristin Labudda Mohamad Javad Norahan Lisa-Marie Hübner Philipp Althoff Klaus Gerwert Mathias Lübben Till Rudack Carsten Kötting A second photoactivatable state of the anion-conducting channelrhodopsin GtACR1 empowers persistent activity Communications Biology |
| title | A second photoactivatable state of the anion-conducting channelrhodopsin GtACR1 empowers persistent activity |
| title_full | A second photoactivatable state of the anion-conducting channelrhodopsin GtACR1 empowers persistent activity |
| title_fullStr | A second photoactivatable state of the anion-conducting channelrhodopsin GtACR1 empowers persistent activity |
| title_full_unstemmed | A second photoactivatable state of the anion-conducting channelrhodopsin GtACR1 empowers persistent activity |
| title_short | A second photoactivatable state of the anion-conducting channelrhodopsin GtACR1 empowers persistent activity |
| title_sort | second photoactivatable state of the anion conducting channelrhodopsin gtacr1 empowers persistent activity |
| url | https://doi.org/10.1038/s42003-025-08560-4 |
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