Searchable abstracts of presentations at key conferences in endocrinology

ea0059apw1.3 | GPCRS: hotspots and complexes | SFEBES2018

The nanodomain organization of GPCR signalling: lessons from TSH receptors and beyond

Calebiro Davide

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...

ea0035mte14 | (1) | ECE2014

Real-time monitoring of GPCR signalling in living cells

Calebiro Davide

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 ...

ea0070ap2 | The European Journal of Endocrinology Prize Lecture | ECE2020

Shining light on membrane receptors

Calebiro Davide

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...

ea0070ap2biog | The European Journal of Endocrinology Prize Lecture | ECE2020

EJE Award 2020 – Biography

Calebiro Davide

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 ...

ea0065p174 | Metabolism and Obesity | SFEBES2019

Impact of free fatty acid 4 receptor internalization on signalling

Tripp Emma , O'Brien Shannon , Calebiro Davide

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...

ea0049oc4.4 | Thyroid Disease 1 | ECE2017

The TSH receptor reaches the trans-Golgi network to induce PKA activation and trigger gene transcription

Godbole Amod , Lyga Sandra , Leo Martina , Calebiro Davide

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(...

ea0041gp189 | Thyroid - Basic | ECE2016

A new paradigm of TSH receptor signaling in the trans-Golgi network

Godbole Amod , Lyga Sandra , Lohse Martin J , Calebiro Davide

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...

ea0016s14.1 | Basic highlights | ECE2008

Direct visualization of cyclic AMP levels in three dimensional cultures of thyroid follicles

Calebiro Davide , Nikolaev Viacheslav , Bonomi Marco , Persani Luca , Lohse Martin

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....

ea0016p693 | Thyroid | ECE2008

Effects of 8-Cl-cAMP on growth and apoptotic process in poorly differentiated thyroid cancer cell lines

Lucchi Simona , de Filippis Tiziana , Calebiro Davide , Porazzi Patrizia , Spada Anna , Persani Luca

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...

ea0049gp28 | Adrenal 3 | ECE2017

A PRKACB somatic mutation in a cortisol producing adenoma: a new example of protein kinase A activation leading to adrenal Cushing syndrome

Espiard Stephanie , Knape Matthias , Bathon Kerstin , Assie Guillaume , Abid Daniel , Faillot Simon , Calebiro Davide , Herberg Friedrich , Stratakis Constantine , Bertherat Jerome

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...