Endocrine Abstracts

G protein-coupled receptors (GPCRs) are the largest family of membrane receptors and major drug targets. They play a fundamental role in the endocrine system by mediating the effects of several hormones and neurotransmitters. Alterations of GPCR signalling, for instance due to genetic mutations, are responsible for a variety of endocrine diseases ranging from congenital hypothyroidism to Cushing’s syndrome. My group develops innovative optical methods such as fluorescence resonance energy transfer (FRET) and single-molecule microscopy, which allow us to investigate GPCR signalling directly in living cells with unprecedented spatiotemporal resolution. Using this innovative approach, we are investigating some of the most fundamental mechanisms at the basis of GPCR signalling and their involvement in human disease. This led us to discover that GPCRs are not only active at the plasma membrane, as previously strongly believed, but also at intracellular sites. Moreover, our work has contributed to the identification of new genetic alterations responsible for endocrine diseases, including the recent discovery that mutations in the catalytic α subunit of protein kinase A cause cortisol-producing adrenocortical adenomas. Altogether, our findings indicate that GPCR signalling is much more complex and dynamic than previously thought. This not only has major implications for understanding the functioning of this important family of receptors, but might also lead to the development of innovative drugs for common diseases such as diabetes or heart failure.