Control of GPCR Activity, Trafficking, And Localization by Proteins That Interact with GPCRS

Abstract

G protein-coupled receptors (GPCRs) are integral in cell-cell communication and physiology, hence represent one of the most promising areas for drug targets. The regulatory proteins involved include GPCR kinases (GRKs), β-arrestins, scaffold proteins, and regulators of G protein signaling (RGS) proteins that modulate desensitization, internalization, recycling, and degradation of the receptors. Disruptions in GPCR signaling lead to numerous diseases in animals such as neurodegenerative diseases, cardiovascular diseases, and cancer. Animal models are very helpful for the study of GPCR regulation, with sophisticated techniques such as fluorescence microscopy, fluorescence resonance energy transfer (FRET), co-immunoprecipitation, and mass spectrometry applied to the study of receptor interaction and trafficking. GEMMs are used to further explain the physiological roles of GPCR-interacting proteins. The study shows the potential importance of targeting these regulatory proteins as a new way forward beyond traditional GPCR agonists and antagonists. This understanding of GPCR signaling in animals provides a new drug discovery path, with precise modulations at the receptor's activity level to improve treatments on veterinary fronts. This means immense implications for the improvement of animal health through next-generation therapeutics that have much greater specificity and fewer off-target effects.