Endocrine Abstracts

My group investigates the basic mechanisms of G protein-coupled receptor (GPCR) signalling and their alterations in endocrine disease, which we study using innovative microscopy methods such as fluorescence resonance energy transfer (FRET) and single-molecule microscopy. Using these methods, we have demonstrated that GPCRs do not only signal via cyclic AMP at the cell surface but also at intracellular sites (Calebiro et al., PLoS Biology 2009). We have shown that this is requi...

G-protein coupled receptors (GPCRs) constitute the largest family of receptors and mediated the effects of many hormones and neurotransmitters. Whereas GPCRs and their signalling cascades have been intensively studied at the molecular and, more recently, structural level, many important aspects of GPCR signalling remain elusive. A major reason for this resides in the limited spatial and temporal resolution of standard biochemical methods. To overcome these limitations, we and ...

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 fluorescenc...

Davide Calebiro is a Professor of Molecular Endocrinology and Wellcome Trust Senior Research Fellow at the Institute of Metabolism and Systems Research (IMSR) and the Centre of Membrane Proteins and Receptors (COMPARE) of the University of Birmingham.He leads a multidisciplinary research team comprising biologists, chemists, physicists, engineers and computer scientists focusing on the basic mechanisms of G protein-coupled receptor (GPCR) signalling and ...

The free fatty acid 4 receptor (FFA4R) is highly expressed in adipose tissue and other tissues that are involved in metabolic homeostasis, where its pharmacological stimulation improves glucose uptake and insulin sensitivity. Work by our and other groups have revealed that, contrary to textbook knowledge, GPCRs are not only active at the plasma membrane, as previously believed, but also at intracellular sites such as early endosomes or the Golgi complex/trans-Golgi network. Ho...

Whereas G-protein coupled receptors (GPCRs) have long been believed to signal via cyclic AMP (cAMP) exclusively at the cell surface, our group has shown that GPCRs also stimulate cAMP production from the cell interior once internalized together with their ligands. This phenomenon, which we originally described for the thyroid stimulating hormone receptor (TSHR) in thyroid follicles, has now also been shown for several other GPCRs. However, the involved subcellular compartment(...

Whereas G-protein coupled receptors (GPCRs) have been long believed to signal through cyclic AMP exclusively at cell surface, our group has previously shown that GPCRs not only signal at the cell surface but can also continue doing so once internalized together with their ligands, leading to persistent cAMP production. This phenomenon, which we originally described for the thyroid stimulating hormone receptor (TSHR) in thyroid cells, has been observed also for other GPCRs. How...

Cyclic AMP (cAMP) is the principal intracellular mediator of TSH effects in the thyroid, inducing both thyroid hormone production and cell proliferation. This notion derives from a large series of evidences, mainly obtained by biochemical approaches on cell lines or primary thyrocytes. However, given the limited resolution in time and space of the techniques employed so far, little is know about the spatial localization and temporal dynamics of cAMP signaling in thyroid cells....

Tools that are highly effective in the treatment of differentiated thyroid cancer (DTC) loose their therapeutic potentials in poorly differentiated tumors. The synthetic analog 8-Cl-cAMP has been known to have an antiproliferative effect in a variety of cancer cells and is tested as antineoplastic agent in clinical trials. The signaling mechanisms that govern the 8-Cl-cAMP-induced growth inhibition are still uncertain and data in thyroid neoplasia are lacking. Therefore, we te...

Introduction: Alterations of the cAMP signaling pathway are described in adrenal tumors causing Cushing syndrome, specifically mutations in the gene coding for the protein kinase A (PKA) catalytic subunit alpha (PRAKCA) in cortisol producing adenomas (CPA) with overt Cushing syndrome.Materiel and Methods: Eight CPAs without PRKACA mutations were analyzed by whole exome sequencing. Direct sequencing of PRAKCB encoding for the catalytic subunit beta (C&#94...