A5047977001- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Ion channel regulation and function
- Muscle Physiology and Disorders
- Myasthenia Gravis and Thymoma
- Pesticide Exposure and Toxicity
- Medicinal Plants and Neuroprotection
- Microfluidic and Bio-sensing Technologies
- Cellular Mechanics and Interactions
- Chemical Reactions and Isotopes
- Diet and metabolism studies
- Enzyme function and inhibition
- 3D Printing in Biomedical Research
- Neurotransmitter Receptor Influence on Behavior
- Wnt/β-catenin signaling in development and cancer
- Cellular transport and secretion
- Chemical synthesis and alkaloids
- Neuropeptides and Animal Physiology
- bioluminescence and chemiluminescence research
- Neurogenetic and Muscular Disorders Research
- Gastrointestinal motility and disorders
- Nerve injury and regeneration
- Muscle activation and electromyography studies
- Neuroscience and Neuropharmacology Research
- Pluripotent Stem Cells Research
Centre National de la Recherche Scientifique
2011-2023
Université Paris Cité
2011-2023
SPPIN - Saints-Pères Paris Institute for Neurosciences
2019-2023
Institut de Psychiatrie et Neurosciences de Paris
2020-2023
Centre de Neurophysique Physiologie et Pathologie
2015-2022
Sorbonne Paris Cité
2012-2022
Délégation Paris 5
2008-2021
Inserm
1983-2011
Laboratoire de Géologie de l’École Normale Supérieure
1988-2008
École Normale Supérieure - PSL
1991-2004
We report the first case of a human neuromuscular transmission dysfunction due to mutations in gene encoding muscle-specific receptor tyrosine kinase (MuSK). Gene analysis identified two heteroallelic mutations, frameshift mutation (c.220insC) and missense (V790M). The muscle biopsy showed dramatic pre- postsynaptic structural abnormalities junction severe decrease acetylcholine (AChR) ε-subunit MuSK expression. In vitro vivo expression experiments were performed using mutant reproducing...
The collagen-tailed or asymmetric forms (A) represent a major component of acetylcholinesterase (AChE) in the neuromuscular junction higher vertebrates. They are hetero-oligomeric molecules, which tetramers catalytic subunits type T (AChE<sub>T</sub>) attached to triple-stranded collagen "tail." We report cloning rat AChE-associated subunit, Q. show that tails encoded by single gene, <i>COLQ</i>. ColQ form homotrimers and readily AChE, when coexpressed with AChE<sub>T</sub>. found same...
At the neuromuscular junction, acetylcholinesterase (AChE) is mainly present as asymmetric forms in which tetramers of catalytic subunits are associated to a specific collagen, collagen Q (ColQ). The accumulation enzyme synaptic basal lamina strictly relies on ColQ. This has been shown be mediated by interaction between ColQ and perlecan, itself binds dystroglycan. Here, using transfected mutants ColQ-deficient muscle cell line or COS-7 cells, we report that clusterizes through more complex...
Neuromuscular junction (NMJ) formation requires the highly coordinated communication of several reciprocal signaling processes between motoneurons and their muscle targets. Identification early, spatially restricted cues in target recognition at NMJ is still poorly documented, especially mammals. Wnt one key pathways regulating synaptic connectivity. Here, we report that Wnt4 contributes to vertebrate vivo. Results from a microarray screen quantitative RT-PCR demonstrate expression regulated...
The muscle-specific kinase MuSK is one of the key molecules orchestrating neuromuscular junction (NMJ) formation. interacts with Wnt morphogens, through its Frizzled-like domain (cysteine-rich [CRD]). Dysfunction CRD in patients has been recently associated onset myasthenia, common disorders mainly characterized by fatigable muscle weakness. However, physiological role Wnt-MuSK interaction NMJ formation and function remains to be elucidated. Here, we demonstrate that deletion mice caused...
Abstract: We obtained a cDNA clone encoding one type of catalytic subunit acetylcholinesterase (AChE) from rat brain (T subunit). The coding sequence shows high frequency (G + C) at the third position codons (66%), as already noted for several AChEs, in contrast with mammalian butyrylcholinesterase. predicted primary AChE presents only 11 amino acid differences, including signal peptide, that mouse T subunit. In particular, four alanines are replaced by serine or threonine. northern blots,...
Abstract Mammalian spinal motoneurons are cholinergic neurons that have long been suspected to use also glutamate as a neurotransmitter. We report VGLUT1 and VGLUT2, two subtypes of vesicular transporters, expressed in rat motoneurons. Both proteins present somato‐dendritic compartments well axon terminals primary cultures immunopurified sections cord from adult rat. However, VGLUT2 not found at neuromuscular junctions skeletal muscles. After intracellular injection biocytin motoneurons, is...
CollagenQ (ColQ) plays an important structural role at vertebrate neuromuscular junctions (NMJs) by anchoring and accumulating acetylcholinesterase (AChE) in the extracellular matrix (ECM). Moreover, ColQ interacts with perlecan/dystroglycan muscle-specific receptor tyrosine kinase (MuSK), key molecules NMJ formation. MuSK promotes acetylcholine (AChR) clustering a process mediated rapsyn, cytoplasmic protein that stimulates AChR packing clusters regulates synaptic gene transcription. Here,...
Understanding the developmental steps shaping formation of neuromuscular junction (NMJ) connecting motoneurons to skeletal muscle fibers, is critical. Wnt morphogens are key players in this specialized peripheral synapse. Yet, individual and collaborative functions Wnts as well their downstream pathways remain poorly understood at NMJ. Here, we demonstrate through Wnt4 Wnt11 gain function studies culture or mice that enhance acetylcholine receptor (AChR) clustering motor axon outgrowth. In...
We studied the splicing and compartmentalization of acetylcholinesterase (AchE) mRNAs during muscle differentiation in mouse, both vitro vivo. used polymerase chain reaction (PCR) to analyse AChE cultures myogenic C2 Sol8 cell lines, developing diaphragm, from embryonic day 14 (E14). characterized three types alternatively spliced mRNAs, encoding catalytic subunits that differ by their C-terminal regions (R, H T). The T transcript is predominant all cases represents only mRNA adult muscle....
The collagen-tailed forms of acetylcholinesterase (AChE) are accumulated at mammalian neuromuscular junctions. A 4 , 8 and 12 expressed differently in the rat fast slow muscles; sternomastoid muscle contains essentially form end plates, whereas soleus also extrajunctional forms. We show that collagen Q (ColQ) transcripts become exclusively junctional adult but remain uniformly soleus. By coinjecting Xenopus oocytes with AChE T ColQ mRNAs, we reproduced patterns ColQ1 ColQ1a, only ColQ1a....
We amplified by PCR and characterized a fragment of cDNA from rat spleen, encoding the distinctive C‐terminal region acetylcholinesterase (AChE) H subunit. A recombinant vector this subunit was constructed expressed in COS cells: subunits produced glycophosphatidylinositol (GPI)‐anchored dimers, showing that spleen contained functional GPI cleavage/attachment site. Using PCR, we did not detect mRNAs AChE muscle or hypothalamus. In liver 16‐day embryos, found both T transcripts, agreement...
Collagen Q (ColQ) is a nonfibrillar collagen that plays crucial role at the vertebrate neuromuscular junction (NMJ) by anchoring acetylcholinesterase to synapse. ColQ also functions in signaling, as it regulates acetylcholine receptor clustering and synaptic gene expression, manner dependent on muscle-specific kinase (MuSK), key protein NMJ formation maintenance. MuSK forms complex with low-density lipoprotein receptor-related 4 (LRP4), its coreceptor for proteoglycan agrin NMJ. Previous...
The collagen ColQ anchors acetylcholinesterase (AChE) in the synaptic cleft of neuromuscular junction (NMJ). It also binds MuSK and perlecan/dystroglycan, 2 signaling platforms postsynaptic domain. Mutations cause a congenital myasthenic syndrome (CMS) with AChE deficiency. Because absence does not fully explain complexity there is no curative treatment for disease, we explored additional potential targets by conducting large genetic screening ColQ-deficient mice, model CMS deficiency,...