A Bright Future? A Perspective on Class C GPCR Based Genetically Encoded Biosensors

One of the major challenges in molecular neuroscience today is to accurately monitor neurotransmitters, neuromodulators, peptides, and various other biomolecules in the brain with high temporal and spatial resolution. Only a comprehensive understanding of neuromodulator dynamics, their release probability, and spatial distribution will unravel their ultimate role in cognition and behavior. This Perspective offers an overview of potential design strategies for class C GPCR-based biosensors. It briefly highlights current applications of GPCR-based biosensors, with a primary focus on class C GPCRs and their unique structural characteristics compared with other GPCR subfamilies. The discussion offers insights into plausible future design approaches for biosensor development targeting members of this specific GPCR subfamily. It is important to note that, at this stage, we are contemplating possibilities rather than presenting a concrete guide, as the pipeline is still under development.