A5087569154- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neural Engineering
- Photoreceptor and optogenetics research
- Receptor Mechanisms and Signaling
- Olfactory and Sensory Function Studies
- Nicotinic Acetylcholine Receptors Study
- Genetic Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Ear Surgery and Otitis Media
- Adipose Tissue and Metabolism
- Machine Learning in Bioinformatics
- Hippo pathway signaling and YAP/TAZ
- S100 Proteins and Annexins
- Virus-based gene therapy research
- Cellular transport and secretion
- Synthesis of heterocyclic compounds
- Neurobiology and Insect Physiology Research
- Connexins and lens biology
- Congenital Ear and Nasal Anomalies
- Neurological disorders and treatments
- Gene expression and cancer classification
Institut des Biomolécules Max Mousseron
2016
Neurosciences Institute
2014
New York University
2009-2011
NYU Langone Health
2008
Centre National de la Recherche Scientifique
1996-2007
University College London
2004-2005
MRC Laboratory for Molecular Cell Biology
2004
Medical Research Council
2004
Centre de Recherche en Biologie cellulaire de Montpellier
1999-2001
Université de Montpellier
2000
Abstract Novel mRNA isoforms for two members of the group III metabotropic glutamate receptors (mGluRs), called mGluR7 b and mGluR8 , were identified from rat brain cerebral cortex hippocampus. In both cases, alternative splicing is generated by a similar out‐of‐frame insertion in carboxyl‐terminus that results replacement last 16 amino acids 23 different acids, respectively. Distribution analysis revealed splice variants are generally coexpressed same areas. The few exceptions olfactory...
Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited degenerative disorder of the cerebellum characterized by nearly selective and progressive death Purkinje cells. The underlying mutation in SCA6 consists an expansion trinucleotide CAG repeat 3' region gene, CACNA1A, encoding alpha(1A) subunit neuronal P/Q-type voltage-gated calcium channel. Although it known that this results expanded tract glutamine residues some splice forms, distribution these forms role highly cell...
Together with the calcium-sensing receptor, metabotropic glutamate receptors (mGluRs) share no sequence homology other G protein-coupled (GPCRs) and therefore constitute a new family of receptors. Recently, it was reported that alpha 15 16 subunits allow many GPCRs to activate phospholipase C (PLC). Furthermore, exchange few carboxyl-terminal residues q by those 12 or o allows resulting chimeric (G ql qol respectively) couple Gi-coupled PLC. We report mGluR2 mGluR4, two negatively coupled...
Cadherins function in the adhesion of presynaptic and postsynaptic membranes at excitatory synapses. Here we show that cadherin-associated protein neural plakophilin-related arm (NPRAP; also called δ-catenin) binds via a density-95 (PSD-95)/discs large/zona occludens-1 (PDZ) interaction to AMPA receptor (AMPAR)-binding (ABP) related glutamate (GluR)-interacting (GRIP), two multi-PDZ proteins bind GluR2 GluR3 AMPAR subunits. The resulting cadherin–NPRAP–ABP/GRIP complexes serve as anchorages...
Regulated transport and local translation of mRNA in neurons are critical for modulating synaptic strength, maintaining proper neural circuitry, establishing long term memory. Neuronal RNA granules ribonucleoprotein particles that serve to along microtubules control protein synthesis response activity. Studies suggest neuronal share similar structures functions with somatic P-bodies. We recently reported the Huntington disease huntingtin (Htt) associates Argonaute (Ago) localizes cytoplasmic...
The proteolytic machinery comprising metalloproteases and γ-secretase, an intramembrane aspartyl protease involved in Alzheimer's disease, cleaves several substrates addition to the extensively studied amyloid precursor protein. Some of these substrates, such as N-cadherin, are synaptic proteins synapse remodeling maintenance. Here we show, rats mice, that γ-secretase physiologic regulators synapses. Both proteases synaptic, with tethered at by δ-catenin, a scaffolding protein also binds...
During sustained depolarization, voltage-gated Ca2+ channels progressively undergo a transition to nonconducting, inactivated state, preventing overload of the cell. This can be triggered either by membrane potential (voltage-dependent inactivation) or consecutive entry Ca2+(Ca2+-dependent inactivation), depending on type channel. These two types inactivation are suspected arise from distinct underlying mechanisms, relying specific molecular sequences different pore-forming channel subunits....
Ca(2+) channel inactivation is a key element in controlling the level of entry through voltage-gated channels. Interaction between pore-forming alpha(1) subunit and auxiliary beta known to be strong modulator voltage-dependent inactivation. Here, we demonstrate that an N-terminal membrane anchoring site (MAS) beta(2a) strongly reduces alpha(1A) (Ca(V)2.1) This effect can mimicked by addition transmembrane segment N terminus subunit. Inhibition also requires link MAS another important...
Metabotropic glutamate (mGlu), Ca<sup>2+</sup>-sensing, γ-aminobutyric acid<sub>B</sub>, and a large number of pheromone receptors constitute peculiar family G protein-coupled receptors. They possess extracellular domain that has been proposed to their ligand binding domain. The aim the current study was examine whether this had any influence on protein-coupling selectivity receptor, vice versa. We chose mGlu receptors, which are classified into three groups according sequence homology...
1 Stargazin or γ2, the product of gene mutated in stargazer mouse, is a homologue γ1 protein, an accessory subunit skeletal muscle L-type Ca2+ channel. γ2 selectively expressed brain, and considered to be putative neuronal channel based mainly on homology γ1. Two new members γ family brain have recently been identified: γ3 γ4. 2 We co-expressed, Xenopus oocytes, human γ2,γ3 γ4 subunits with P/Q-type (CaV2.1) different regulatory (α2-δ; β1, β2, β3 β4). 3 Subcellular distribution confirmed...
GABA(B) receptors are heterodimeric G protein-coupled that mediate slow synaptic inhibition in the central nervous system. Whereas heterodimerization between receptor GABA(B)R1 and GABA(B)R2 subunits is essential for functional expression, how neurons coordinate assembly of these critical remains to be established. Here we have identified Marlin-1, a novel receptor-binding protein associates specifically with subunit yeast, tissue culture cells, neurons. Marlin-1 expressed brain exhibits...
Ca2+ current potentiation by conditioning depolarization is a general mechanism which excitable cells can control the level of entry during repetitive depolarizations. Several types channels are sensitive to depolarization, however, using clearly distinguishable mechanisms. In case L-type channels, prepulse-induced facilitation only be recorded when pore-forming α1C subunit coexpressed with auxiliary β1, β3, or β4, but not β2, subunit. These four β subunits composed two conserved domains...
Ca 2+ channel auxiliary β subunits have been shown to modulate voltage‐dependent inactivation of various types channels. The 1 and 2 subunits, that are differentially expressed with the L‐type α subunit in heart, muscle brain, can specifically ‐dependent kinetics. Their expression Xenopus oocytes 1C leads, both cases, biphasic current decays, second phase being markedly slowed by subunit. Using a series deletion mutants chimeric constructs we show inhibitory site located on amino‐terminal...
This article describes a study designed to assess the feasibility of using recombinant adenovirus for delivering therapeutic peptides in vivo guinea pig middle ear cleft. A adenoviral vector AdCMVsp1 LacZ containing Escherichia coli β-galactosidase was injected into space. Qualitative assessment cell transfection performed on day 2 by light microscopy study, after injecting multiplicity infection (MOI) ranging from 0 1000. At an MOI 30, 30% promontory area epithelial cells were stained. An...
The effects of 2,5-di(<i>tert</i>-butyl)-1,4-benzohydroquinone (tBHQ), a synthetic phenolic antioxidant and blocker the sarco-endoplasmic ATPase, were evaluated on low high voltage-activated Ca<sup>2+</sup> currents (ICas) with rodent dorsal root ganglion, hippocampal, motor neurons. In all cell types tested, tBHQ (IC<sub>50</sub> = 35 μM) blocked ICa at concentrations used to inhibit ATPase. This effect was specific because other reticulum calcium ATPase pump inhibitors (thapsigargin...
Our group has been interested in the structure and function of voltage-gated Ca2+ channels since many years. We have tried to combine molecular cloning, site-directed mutagenesis, heterologous expression, electrophysiological recordings fluorescence imaging identify structures motions understand mechanisms that are responsible for several biophysical properties these channels. In this talk I will present you a brief overview work with special emphasis on voltage-dependent inactivation...
Gamma-secretase, which generates amyloid peptide from APP, also cleaves other type I transmembrane proteins, including synaptic proteins such as N-cadherin. The cleavage pathway involves initial ectodomain shedding by a metalloprotease, followed intramembrane gamma-secretase. C-terminal fragments generated the of several gamma-secretase substrates can have signaling functions and regulate transcription (Hass et al., 2009)1. We previously shown existence activity-dependent APP N-cadherin...
Familial cases of AD (FAD) result from mutations in APP and presenilin 1 2 (PS1 2) proteins. PS are thought to be the catalytic subunit gamma secretase, thus function generation amyloid peptide APP. However, secretase also cleaves other type I transmembrane proteins, including Notch, Cadherin ErbB4. Other binding partners PS1 have been identified. One these, NPRAP (delta catenin), has shown interact with ABP (AMPA receptor protein), by our lab. Thus, could a more ubiquitous degrading...