Light-activated chimeric GPCRs: limitations and opportunities. (August 2019) - Tichy, Alexandra-Madelaine
Graphical abstract: Highlights: Optogenetics can control biological processes with high spatio-temporal precision. Light-activated GPCRs (OptoXRs) were developed using chimeric protein engineering. OptoXRs were used to activate GPCR signalling ex vivo and in vivo. Open questions include the signalling specificity and bias of OptoXRs. Next-generation OptoXRs will have optimized and broader functionality. Abstract : Light-activated chimeric GPCRs, termed OptoXRs, can elicit cell signalling responses with the high spatial and temporal precision of light. In recent years, an expanding OptoXR toolkit has been applied to, for example, dissect neural circuits in awake rodents, guide cell migration during vertebrate development and even restore visual responses in a rodent model of blindness. OptoXRs have been further developed through incorporation of highly sensitive photoreceptor domains and a plethora of signalling modules. The availability of new high-resolution structures of GPCRs and a deeper understanding of GPCR function allows critically revisitation of the design of OptoXRs. Next-generation OptoXRs will build on advances in structural biology, receptor function and photoreceptor diversity to manipulate GPCR signalling with unprecedented accuracy and precision.