A5029033857- Ion channel regulation and function
- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Genetic Neurodegenerative Diseases
- Cardiac electrophysiology and arrhythmias
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Agriculture and Rural Development Research
- Adipose Tissue and Metabolism
- Plant Physiology and Cultivation Studies
- CRISPR and Genetic Engineering
- Cardiovascular Effects of Exercise
- Ion Channels and Receptors
- Postharvest Quality and Shelf Life Management
- Caveolin-1 and cellular processes
- Neuroscience and Neuropharmacology Research
- Plant tissue culture and regeneration
- Lipid Membrane Structure and Behavior
- Pharmacological Effects and Assays
- Neurogenetic and Muscular Disorders Research
- Horticultural and Viticultural Research
- Plant Gene Expression Analysis
- Plant Molecular Biology Research
- Calcium signaling and nucleotide metabolism
- Nuclear Structure and Function
Grenoble Institute of Neurosciences
2016-2025
Inserm
2016-2025
Université Grenoble Alpes
2010-2025
Centre Hospitalier Universitaire de Grenoble
2007-2025
University of California, Davis
2017
Bern University of Applied Sciences
2016
Université Joseph Fourier
2005-2015
Fondazione Salvatore Maugeri
2014
CEA Grenoble
1998-2013
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
1998-2013
est destinée au dépôt et à la diffusion de documents scientifiques niveau recherche, publiés ou non, émanant des établissements d'enseignement recherche français étrangers, laboratoires publics privés.
The main histological abnormality in congenital fiber type disproportion (CFTD) is hypotrophy of 1 (slow twitch) fibers compared to 2 (fast fibers. To investigate whether mutations RYR1 are a cause CFTD we sequenced seven families whom the other known causes had been excluded. We identified compound heterozygous changes gene four (five patients), consistent with autosomal recessive inheritance. Three out five patients ophthalmoplegia, which may be most specific clinical indication RYR1. Type...
The skeletal muscle ryanodine receptor is an essential component of the excitation–contraction coupling apparatus. Mutations in RYR1 are associated with several congenital myopathies (termed RYR1-related myopathies) that most common non-dystrophic diseases childhood. Currently, no treatments exist for these disorders. Although primary pathogenic abnormality involves defective coupling, other abnormalities likely play a role disease pathogenesis. In effort to discover novel mechanisms, we...
Abstract Mutations in amphiphysin‐2/ BIN 1, dynamin 2, and myotubularin are associated with centronuclear myopathy ( CNM ), a muscle disorder characterized by myofibers atypical central nuclear positioning abnormal triads. Mis‐splicing of 1 is also myotonic dystrophy that shares histopathological hallmarks . How amphiphysin‐2 orchestrates triad organization how ‐associated mutations lead to dysfunction remains elusive. We find N‐ WASP interacts this interaction distribution disrupted...
Background— Catecholaminergic polymorphic ventricular tachycardia is an inherited arrhythmogenic disorder characterized by sudden cardiac death in children. Drug therapy still insufficient to provide full protection against arrest, and the use of implantable defibrillators pediatric population limited side effects. There therefore a need explore curative potential gene for this disease. We investigated efficacy durability viral transfer calsequestrin 2 ( CASQ2 ) wild-type catecholaminergic...
Membrane vesicles enriched in both ryanodine receptor and dihydropyridine were obtained from rabbit skeletal muscle solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. Analysis of the sedimentation behavior proteins showed existence a population alpha 1 subunits which cosedimented receptor. Solubilized immunoprecipitated antibodies directed against either or 1, 2, beta Immunoprecipitated identified by Western blot analysis specific labeling [3H]ryanodine...
The ryanodine receptor (RYR1) is an essential component of the calcium homeostasis skeletal muscle in mammals. Inactivation RYR1 gene mice lethal at birth. In humans only missense and in-frame mutations have been associated so far with various disorders including malignant hyperthermia, central core disease moderate form multi-minicore (MmD). We identified a cryptic splicing mutation that resulted 90% decrease normal transcript muscle. 14646+2.99 kb A→G was classical MmD ophthalmoplegia,...
An emerging concept is that a neuronal isoform of nitric oxide synthase (NOS1) may regulate myocardial contractility. However, role for NOS1-derived (NO) in heart failure (HF) has not been defined.Using model infarction-induced HF, we demonstrated cardiac NOS1 expression and activity increased HF rats (P<0.05 P<0.001 versus shams, respectively). This was associated with translocation from the ryanodine receptor to sarcolemma through interactions caveolin-3 hearts. With ex vivo...
In order to elucidate the regulation mechanisms of carotenoid biosynthesis in apricot fruit (Prunus armeniaca), content and carotenogenic gene expression were analysed as a function ethylene production two colour-contrasted varieties. Fruits from Goldrich (GO) orange, while Moniqui (MO) fruits white. Biochemical analysis showed that GO accumulated precursors uncoloured carotenoids, phytoene phytofluene, coloured carotenoid, beta-carotene, only phytofluene but no beta-carotene. Physiological...
Tomato texture is one of the critical components for consumer's perception fruit quality. Texture a complex character composed several attributes that are difficult to evaluate and which change during ripening. This study investigated tomato fruits at rheological, sensory, morphological, genetic levels, attempted correlate parameters. Analyses were performed on from introgressed lines carrying quantitative trait loci (QTLs) associated with traits localized different chromosomes, in two...
J. A. Bevilacqua, N. Monnier, M. Bitoun, B. Eymard, Ferreiro, S. Monges, F. Lubieniecki, L. Taratuto, Laquerrière, K. G. Claeys, I. Marty, Fardeau, P. Guicheney, Lunardi and Romero (2011) Neuropathology Applied Neurobiology37, 271–284Recessive RYR1 mutations cause unusual congenital myopathy with prominent nuclear internalization large areas of myofibrillar disorganization Aims: To report the clinical, pathological genetic findings in a group patients previously not described phenotype due...
Mutations of the ryanodine receptor cause dominant and recessive forms congenital myopathies with cores. Quantitative defects RYR1 have been reported in families presenting disease epigenic regulation has recently proposed to explain potential maternal monoallelic silencing gene. We investigated nine a form showing quantitative defect expression. Genetic analysis allowed identification mutation on both alleles gene for all patients, 15 being novel variants. evidenced patients an alteration...
Excitation-contraction coupling requires a highly specialized membrane structure, the triad, composed of plasma invagination, T-tubule, surrounded by two sarcoplasmic reticulum terminal cisternae. Although precise mechanisms governing T-tubule biogenesis and triad formation remain largely unknown, studies have shown that caveolae participate in mutations several their constituents induce muscle weakness myopathies. Here, we demonstrate that, at membrane, Bin1 caveolin-3 assemble into...
Defects in cardiomyocyte Ca(2+) cycling are a signature feature of heart failure (HF) that occurs response to sustained hemodynamic overload, and they largely account for contractile dysfunction. Neuronal nitric oxide synthase (NOS1) influences myocyte excitation-contraction coupling through modulation cycling, but the potential relevance this HF is unknown.We generated transgenic mouse with conditional, cardiomyocyte-specific NOS1 overexpression (double-transgenic [DT]) studied cardiac...
Triadin is a multiple proteins family, some isoforms being involved in muscle excitation-contraction coupling, and having still unknown functions. To obtain clues on triadin functions, we engineered knock-out mouse line characterized the physiological effect of ablation skeletal function. These mice presented reduced strength, which seemed not to alter their survival has been present work. We first checked these expression level different calcium homeostasis observed fast muscles an increase...
Distal arthrogryposis (DA) is a heterogeneous subgroup of multiplex congenita (AMC), large family disorders characterized by multiple congenital joint limitations due to reduced fetal movements. DA mainly contractures afflicting especially the distal extremities without overt muscular or neurological signs. Although limited number genes mostly implicated in contractile apparatus have been identified DA, most patients failed show mutations currently known genes. Using pangenomic approach, we...
Congenital myopathies are severe muscle disorders affecting adults as well children in all populations. The diagnosis of congenital is constrained by strong clinical and genetic heterogeneity. Moreover, the majority patients present with unspecific histological features, precluding purposive molecular demonstrating need for an alternative more efficient diagnostic approach. We used exome sequencing complemented ultrastructural analysis biopsies to identify causative mutations eight...
The excitation-contraction coupling process of human atrial myocytes was studied in voltage-clamped isolated from right appendages obtained during cardiac surgery. Intracellular Ca2+ transients (Cai transients) were monitored with 0.1 mmol/L indo 1 added to the internal dialyzing solution. Ryanodine receptors (RyRs) and sarcomeric alpha-actinin stained specific antibodies visualized using plane confocal microscopy. L-Type current (Ica) elicited a prolonged Cai transient, an initial rapidly...
In striated muscles, Ca# + release from internal stores through ryanodine receptor (RyR) channels is triggered by functional coupling to voltage-activated known as dihydropyridine receptors (DHPRs) located in the plasma membrane.In skeletal muscle, this occurs a direct conformational link between tissue-specific DHPR (Ca v 1.1) and RyR ", whereas heart signal carried cardiac-type 1.2) # calcium ions acting an activator.Subtypes of both are expressed central nervous system, but their...
Despite intensive interest in the dedifferentiation process of vascular smooth muscle cells, very little data are available on intracellular Ca(2+) signaling. The present study was designed to investigate evolution pools when rat aortic cells (RASMCs) proliferate and define mechanisms involved functional alterations. RASMCs were cultured different conditions, [Ca(2+)](i) measured by use fura 2. Expression sarco(endo)plasmic reticulum pumps (SERCA2a SERCA2b), channels, ryanodine receptor...
Defective calcium (Ca2+) signaling and impaired contractile function have been observed in skeletal muscle secondary to myocardial function. However, the molecular basis for these defects not identified. In this study, we evaluated alterations of ryanodine-sensitive Ca2+ release channels (RyR1) by analyzing global local a rat postmyocardial infarction (PMI) model overload. transients, measured with multiphoton imaging individual fibers within whole extensor digitorum longus (EDL) muscle,...
Ca2+ release from intracellular stores is controlled by complex interactions between multiple proteins. Triadin a transmembrane glycoprotein of the junctional sarcoplasmic reticulum striated muscle that interacts with both calsequestrin and type 1 ryanodine receptor (RyR1) to communicate changes in luminal machinery. However, potential impact triadin association RyR1 skeletal excitation–contraction coupling remains elusive. Here we show binding critically important for rapid during coupling....