A5027347875- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Neuropeptides and Animal Physiology
- Pancreatic function and diabetes
- Advanced Fluorescence Microscopy Techniques
- Neuroscience and Neuropharmacology Research
- Monoclonal and Polyclonal Antibodies Research
- Bipolar Disorder and Treatment
- Lipid Membrane Structure and Behavior
- Schizophrenia research and treatment
- Attention Deficit Hyperactivity Disorder
- Pharmacological Effects and Toxicity Studies
- Diabetes Treatment and Management
- Photoreceptor and optogenetics research
- Protein Kinase Regulation and GTPase Signaling
- Circadian rhythm and melatonin
- Treatment of Major Depression
- Epilepsy research and treatment
- Pharmacological Receptor Mechanisms and Effects
- Cell Image Analysis Techniques
- Genetic Neurodegenerative Diseases
- Advanced Biosensing Techniques and Applications
- Single-cell and spatial transcriptomics
- Adenosine and Purinergic Signaling
- Peripheral Nerve Disorders
University of Pisa
2016-2025
National Institute of Diabetes and Digestive and Kidney Diseases
2009-2017
University of L'Aquila
2017
École Polytechnique Fédérale de Lausanne
2010-2014
Institute of Bioorganic Chemistry
2010
National Institutes of Health
2005-2009
National Heart Lung and Blood Institute
2008
Impaired functioning of pancreatic β cells is a key hallmark type 2 diabetes. cell function modulated by the actions different classes heterotrimeric G proteins. The functional consequences activating specific protein signaling pathways in vivo are not well understood at present, primarily due to fact that protein-coupled receptors (GPCRs) also expressed many other tissues. To circumvent these difficulties, we developed chemical-genetic approach allows for conditional and selective...
In this work we discuss how to use photophysical information for improved quantitative measurements using Photo Activated Localization Microscopy (PALM) imaging. We introduce a method that reliably estimates the number of photoblinking molecules present in biological sample and gives robust way quantify proteins at single-cell level from PALM images. apply determine amount β2 adrenergic receptor, prototypical G Protein Coupled Receptor, expressed on plasma membrane HeLa cells.
Evidence for heterodimerization has recently been provided dopamine D(1) and adenosine A(1) receptors as well D(2) somatostatin SSTR(5) receptors. In this paper, we have studied the possibility that D(3) interact functionally by forming receptor heterodimers. Initially, split two at level of third cytoplasmic loop into fragments. The first, containing transmembrane domains (TM) I to V N-terminal part loop, was named D(2trunk) or D(3trunk), second, C-terminal TMVI TMVII, tail, D(2tail)...
Recent studies suggest that the second extracellular loop (o2 loop) of bovine rhodopsin and other class I G protein-coupled receptors (GPCRs) targeted by biogenic amine ligands folds deeply into transmembrane receptor core where binding <i>cis</i>-retinal is known to occur. In past, potential role o2 in agonist-dependent activation GPCRs has not been studied systematically. To address this issue, we used M<sub>3</sub> muscarinic acetylcholine (M3R), a prototypic GPCR, as model system....
Although agonist-dependent endocytosis of G protein-coupled receptors (GPCRs) as a means to modulate receptor signaling has been widely studied, the constitutive GPCRs received little attention. Here we show that two prototypical class I GPCRs, β2 adrenergic and M3 muscarinic receptors, enter cells constitutively by clathrin-independent colocalize with markers this endosomal pathway on recycling tubular endosomes, indicating these can subsequently recycle back plasma membrane (PM). This was...
Illumination with 405 nm light can recover the emission for single green fluorescent protein (GFP) mutants that have gone into a long-lived dark state. The reported behavior is standard reverse photoswitchable Dronpa and its mutants. However, conventional knowledge regarding mEos2 photoactivatable (PA-FP) that, once bleached, this fluorophore hardly reactivated, aside from minority population might display behavior. Here we show in typical experiment, approximately 50% of investigated...
Recent developments in the field of optical super-resolution techniques allow both a 10-fold increase resolution as well an increased ability to quantify number labeled molecules visualized fluorescence measurement. By using photoactivated localization microscopy (PALM) and experimental approach based on systematic comparison with nonclustering peptide negative control, we found that prototypical G protein-coupled receptor β2-adrenergic is partially preassociated nanoscale-sized clusters...
Psychiatric disorders often require pharmacological interventions to alleviate symptoms and improve quality of life. However, achieving an optimal therapeutic outcome is challenging due several factors, including variability in the individual response, inter-individual differences drug metabolism, interactions polytherapy. Therapeutic monitoring (TDM), by measuring concentrations biological samples, represents a valuable tool address these challenges, tailoring medication regimens each...
Muscarinic acetylcholine receptors are prototypical G protein-coupled (GPCRs), members of a large family 7 transmembrane mediating wide variety extracellular signals. We show here, in cultured cells and murine model, that the carboxyl terminal fragment muscarinic M2 receptor, comprising regions 6 (M2tail), is expressed by virtue an internal ribosome entry site localized third intracellular loop. Single-cell imaging import isolated yeast mitochondria reveals M2tail, whose expression...
Therapeutic strategies that augment insulin release from pancreatic β-cells are considered beneficial in the treatment of type 2 diabetes. We previously demonstrated activation β-cell M 3 muscarinic receptors (M3Rs) greatly promotes glucose-stimulated secretion (GSIS), suggesting aimed at enhancing signaling through M3Rs may become therapeutically useful. M3R leads to stimulation G proteins q family, which under inhibitory control known as regulators protein (RGS proteins). At present, it...
Background/Objectives MC4R expression and its role in colorectal anaplastic thyroid cancers, where resistance to therapy lack of standard treatments remain significant challenges, are poorly understood. This study aimed investigate as a potential therapeutic target these cancers using the selective antagonist ML00253764 (ML), alone combination with vinorelbine (VNR) irinotecan (or active metabolite SN-38). Methods: Human adenocarcinoma HT-29, Caco-2, carcinoma 8305C cell lines were used. was...
Early Huntington's disease (HD) include over-activation of dopamine D1 receptors (D1R), producing an imbalance in dopaminergic neurotransmission and cell death. To reduce D1R over-activation, we present a strategy based on targeting complexes histamine H3 (H3R). Using HD mouse striatal model organotypic brain slices found that D1R-induced death signaling neuronal degeneration, are mitigated by H3R antagonist. We demonstrate the D1R-H3R heteromer is expressed mice at early but not late stages...