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G Protein-Coupled Receptors (GPCRs) signaling in health and disease
MRC Laboratory of Molecular Biology, UK
Cells need to perceive their environment and respond accordingly. Thus signal transduction across the cell membrane is a fundamental biological process that is required to maintain cellular homeostasis and to ensure coordinated cellular activity in all organisms. One of the largest and most diverse membrane protein families is the G... read moreprotein-coupled receptor (GPCR), that are encoded by more than 800 genes in the human genome. GPCRs function by detecting a wide spectrum of extracellular signals, including photons, ions, small organic molecules, peptides and entire proteins. After ligand binding, GPCRs undergo conformational changes. This leads to the activation of complex cytosolic signalling networks via G proteins, arrestins, and other effector molecules, ultimately resulting in a cellular response.
Different members of the family influence almost every aspect of human physiology ranging from the immune to the nervous system, reproductive and hormone systems as well as the sensory responses such as vision, smell and taste. Mutations in GPCRs have been linked with numerous diseases and over 100 GPCRs are already the targets of ~35% of all available drugs in the market. Thus, understanding how GPCRs function at different scales of complexity has the potential to revolutionize human health and society.
Given their importance, studying GPCR signalling has been a highly active area of research, and was recognised by the 2012 Nobel Prize in Chemistry to Robert Lefkowitz and Brian Kobilka. Research into GPCRs has involved scientists from a wide range of disciplines -- biochemists, pharmacologists, structural biologists, cell and molecular biologists, neurobiologists, medics, synthetic biologists, biophysicists, medicinal chemists, chemical biologists, protein engineers, computational biologists, geneticists, and cancer biologists.