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Light-activated chimeric GPCRs: limitations and opportunities

Alexandra-Madelaine Tichy1, Elliot J Gerrard2, Patrick M Sexton3

  • 1Australian Regenerative Medicine Institute (ARMI), Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC 3800, Australia; European Molecular Biology Laboratory Australia (EMBL Australia), Monash University, Clayton, VIC 3800, Australia.

Current Opinion in Structural Biology
|June 18, 2019
PubMed

Insights

Optically activated G protein-coupled receptors (OptoXRs) precisely control cell signaling using light. Future OptoXRs will leverage structural biology and photoreceptor advances for enhanced GPCR manipulation.

Area of Science:

  • Optogenetics
  • Molecular Biology
  • Neuroscience
  • Cell Signaling

Background:

  • Light-activated chimeric G protein-coupled receptors (OptoXRs) enable precise control over cellular signaling pathways with light.
  • Existing OptoXR tools have been successfully used in neuroscience and developmental biology, including restoring vision in rodent models.

Purpose of the Study:

  • To critically revisit and improve the design of OptoXRs by incorporating recent advances in structural biology and GPCR function.
  • To explore the potential of next-generation OptoXRs for highly accurate and precise manipulation of GPCR signaling.

Main Methods:

  • Development of OptoXRs by integrating sensitive photoreceptor domains and diverse signaling modules.
  • Leveraging high-resolution GPCR structures and functional understanding for rational OptoXR design.
  • Exploring diverse photoreceptor components to expand OptoXR capabilities.

Main Results:

  • OptoXRs offer high spatial and temporal precision in eliciting cell signaling responses.
  • Advancements in photoreceptor sensitivity and signaling modules have enhanced OptoXR functionality.
  • New structural and functional insights into GPCRs provide a basis for improved OptoXR design.

Conclusions:

  • Next-generation OptoXRs are poised to offer unprecedented accuracy and precision in manipulating GPCR signaling.
  • The integration of structural biology, receptor function, and photoreceptor diversity will drive future OptoXR development.

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