Scholarlink

<p>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 <i>syn</i>-pathway of its branched photocycle. In contrast, the homologous anion-conducting ACR1 from <i>Guillardia theta</i> (<i>Gt</i>ACR1), exhibits high photocurrents. Here, we investigate the mechanistic cause for the observed high photocurrents in <i>Gt</i>ACR1 using FTIR spectroscopy. Unexpectedly, we discovered that the O intermediate of <i>Gt</i>ACR1 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A second photoactivatable state of the anion-conducting channelrhodopsin GtACR1 empowers persistent activity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月8日

查看全文
  • Kristin Labudda,
  • Mohamad Javad Norahan,
  • Lisa-Marie Hübner,
  • Philipp Althoff,
  • Klaus Gerwert,
  • Mathias Lübben,
  • Till Rudack,
  • Carsten Kötting

摘要

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.