A5014596303- Ion channel regulation and function
- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Ion Channels and Receptors
- Genetic Neurodegenerative Diseases
- Calcium signaling and nucleotide metabolism
- Cardiac electrophysiology and arrhythmias
- Adipose Tissue and Metabolism
- RNA Research and Splicing
- Signaling Pathways in Disease
- Adenosine and Purinergic Signaling
- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Neurobiology and Insect Physiology Research
- Immune cells in cancer
- Hormonal and reproductive studies
- Neuroscience and Neuropharmacology Research
- Birth, Development, and Health
- Mitochondrial Function and Pathology
- Mesenchymal stem cell research
- Tissue Engineering and Regenerative Medicine
- Insect Resistance and Genetics
- Genetic factors in colorectal cancer
- Cellular Mechanics and Interactions
- Cardiovascular Effects of Exercise
University of Siena
2016-2025
Azienda Ospedaliera Universitaria Senese
2014-2025
Institut de Myologie
2013-2014
Institute of Molecular Medicine
2013
San Raffaele University of Rome
1996-1998
Karolinska Institutet
1998
University of Milan
1986-1996
Assembly of specialized membrane domains, both the plasma and ER, is necessary for physiological activity striated muscle cells. The mechanisms that mediate structural organization sarcoplasmic reticulum with respect to myofibrils are, however, not known. We report here ank1.5, a small splice variant ank1 gene localized on membrane, capable interacting sequence 25 aa located at COOH terminus obscurin. Obscurin giant sarcomeric protein ∼800 kD binds titin has been proposed interactions...
The mechanism by which cyclic adenosine diphosphate ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) mobilize intracellular Ca(2+) stores remains controversial. It is open to question whether cADPR regulates ryanodine receptors (RyRs) directly, as originally proposed, or indirectly promoting uptake into the sarco/endoplasmic reticulum Ca(2+)-ATPases. Conversely, although we have proposed that NAADP mobilizes endolysosomal activating two-pore domain channels (TPCs),...
Molecular mechanisms that regulate in situ activation of ryanodine receptors (RY) different cells are poorly understood. Here we demonstrate caffeine (10 mM) released Ca 2+ from the endoplasmic reticulum (ER) form small spikes only 14% cultured fura-2 loaded beta ob/ob mice. Surprisingly, when forskolin, an activator adenylyl cyclase was present, induced larger as many 60% cells. Forskolin or phosphodiesterase-resistant PKA Sp-cAMPS alone did not release ER. 4-Chloro-3-ethylphenol (4-CEP),...
Obscurin is a large myofibrillar protein that contains several interacting modules, one of which mediates binding to muscle-specific ankyrins. Interaction between obscurin and the ankyrin sAnk1.5 regulates organization sarcoplasmic reticulum in striated muscles. Additional isoforms, ankB ankG, are localized at subsarcolemma level, they contribute dystrophin β-dystroglycan costameres. In this paper, we report mice deficient for obscurin, was displaced from its localization M band, whereas...
Here, we report the identification of three novel missense mutations in calsequestrin-1 (CASQ1) gene four patients with tubular aggregate myopathy. These CASQ1 affect conserved amino acids position 44 (p.(Asp44Asn)), 103 (p.(Gly103Asp)), and 385 (p.(Ile385Thr)). Functional studies, based on turbidity dynamic light scattering measurements at increasing Ca2+ concentrations, showed a reduced -dependent aggregation for protein containing p.Asp44Asn p.Gly103Asp slight increase p.Ile385Thr....
A missense mutation in the calsequestrin-1 gene (CASQ1) was found a group of patients with myopathy characterized by weakness, fatigue, and presence large vacuoles containing characteristic inclusions resulting from aggregation sarcoplasmic reticulum (SR) proteins. The affects conserved aspartic acid position 244 (p.Asp244Gly) located one high-affinity Ca(2+) -binding sites CASQ1 alters kinetics release muscle fibers. Expression mutated protein COS-7 cells showed markedly reduced ability...
Abstract Dysregulation of calcium signaling is emerging as a key feature in the pathogenesis neurodegenerative diseases such Alzheimer’s disease (AD), Parkinson’s (PD), and Huntington’s (HD), targeting this process may be therapeutically beneficial. Under perspective, it important to study proteins that regulate homeostasis cell. Sorcin one most expressed calcium-binding human brain; its overexpression increases endoplasmic reticulum (ER) concentration decreases ER stress heart other...
We investigated the interaction of 12kDa FK506-binding protein (FKBP12) with two ryanodine-receptor isoforms (RyR1 and RyR3) myo-inositol 1,4,5-trisphosphate (IP3) receptor (IP3R1 IP3R3). Using glutathione S-transferase (GST)-FKBP12 affinity chromatography, we could efficiently extract RyR1 (42±7% solubilized RyR1) from terminal cisternae skeletal muscle as well RyR3 (32±4% RyR3-overexpressing HEK-293 cells. These interactions were completely abolished by FK506 (20µM) but largely unaffected...
We compared the interaction of FK506-binding protein (FKBP) with type 3 ryanodine receptor (RyR3) and 1 inositol 1,4,5-trisphosphate (IP(3)R1 IP(3)R3), using a quantitative GST-FKBP12 GST-FKBP12.6 affinity assay. first characterized mapped FKBPs RyR3. as well were able to bind approximately 30% solubilized The was completely abolished by FK506, strengthened addition Mg(2+), weakened in absence Ca(2+) but not affected cyclic ADP-ribose. By proteolytic mapping site-directed mutagenesis, we...
A novel FLNC c.5161delG (p.Gly1722ValfsTer61) mutation was identified in two members of a French family affected by distal myopathy and one healthy relative. This is nucleotide away from previously reported (c.5160delC) that patients asymptomatic carriers three Bulgarian families with muscular dystrophy, indicating low penetrance the frameshift mutations. Given these similarities, we believe mutations alone can be causative without full penetrance. Moreover, comparative analysis clinical...
Obscurin is a large muscle protein whose multiple functions include providing mechanical strength to the M-band and linking sarcomere sarcoplasmic reticulum. Mutations in obscurin are linked various forms of diseases. This study compares cardiac function murine model deletion (KO) with wild-type (WT) vivo ex vivo. Echocardiography showed that KO hearts had larger (+20%) end-diastolic end-systolic volumes, reduced fractional shortening, impaired ejection fraction, consistent dilated...
Ryanodine receptors (RyRs) are expressed on the endoplasmic reticulum of many cells, where they form intracellular Ca2+-release channels that participate in generation Ca2+ signals. Here we report studies localisation and functional properties transfected RyR1 or RyR3 HEK 293 cells. Immunofluorescence indicated both did not clusters but were homogeneously distributed throughout reticulum. release experiments showed responded to caffeine, although with different sensitivity,generating a...
1. Confocal laser scanning microscopy was used to monitor Ca2+ signals in primary-cultured myotubes, prepared from forelimbs of wild-type or ryanodine receptor type 3 (RyR3) knockout mice. Myotubes loaded with the acetoxymethyl ester (AM) form fluo-3 were imaged at rest under whole-cell patch clamp. 2. Discrete release events detected intact and RyR3-knockout myotubes. They showed almost no difference amplitude width, but substantially different duration. In myotubes (660 events, 57 cells)...
Muscle-specific ankyrins 1 (sAnk1) are a group of small ankyrin isoforms, which sAnk1.5 is the most abundant. sAnk1 localized in sarcoplasmic reticulum (SR) membrane from where they interact with obscurin, myofibrillar protein. This interaction appears to contribute stabilize SR close myofibrils. Here we report structural and functional characterization skeletal muscles knockout mice (KO). Deletion did not change expression localization proteins 4- 6-mo-old KO mice. Structurally, main...