Expanding the family of genetically encoded voltage indicators with a candidate Heliorhodopsin exhibiting near-infrared fluorescence

Srividya Ganapathy, Xin Meng, Delizzia Mossel, Mels Jagt, Daan Brinks*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

1 Citation (Scopus)
23 Downloads (Pure)


Genetically encoded voltage indicators, particularly those based on microbial rhodopsins, are gaining traction in neuroscience as fluorescent sensors for imaging voltage dynamics with high-spatiotemporal precision. Here we establish a novel genetically encoded voltage indicator candidate based on the recently discovered subfamily of the microbial rhodopsin clade, termed heliorhodopsins. We discovered that upon excitation at 530 to 560 nm, wildtype heliorhodopsin exhibits near-infrared fluorescence, which is sensitive to membrane voltage. We characterized the fluorescence brightness, photostability, voltage sensitivity, and kinetics of wildtype heliorhodopsin in HEK293T cells and further examined the impact of mutating key residues near the retinal chromophore. The S237A mutation significantly improved the fluorescence response of heliorhodopsin by 76% providing a highly promising starting point for further protein evolution.

Original languageEnglish
Article number104771
Number of pages10
JournalJournal of Biological Chemistry
Issue number6
Publication statusPublished - 2023


  • fluorescence microscopy
  • neuroscience
  • protein engineering
  • rhodopsins
  • voltage sensors

Cite this