MuSK frizzled-like domain is critical for mammalian neuromuscular junction formation and maintenance
| Autor: | Julien Messéant, Marin Manuel, Daniel Zytnicki, Alexandre Dobbertin, Laurent Schaeffer, Claire Legay, Alain Schmitt, Perrine Delers, Emmanuelle Girard, Francesca Mangione, Laure Strochlic, Dominique Le Denmat, Jordi Molgó |
|---|---|
| Přispěvatelé: | Centre de neurophysique, physiologie, pathologie (UMR 8119), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathologies, Imagerie et Biothérapies oro-faciales (EA 2496), Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Paris-Saclay (Neuro-PSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Neurophysique et physiologie du système moteur (NPSM), Biologie des Jonctions Neuromusculaires Normales et Pathologiques (U686), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut des Neurosciences Paris-Saclay (NeuroPSI), Association Francaise contre les Myopathies (14960, 18046), Centre National de la Recherche Scientifique, Paris Descartes University, Institut National de la Sante et de la Recherche Medicale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de neurophysique, physiologie, pathologie ( UMR 8119 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Pathologies, Imagerie et Biothérapies oro-faciales ( EA 2496 ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Neurosciences de Paris-Saclay ( Neuro-PSI ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Neurophysique et physiologie du système moteur ( NPSM ), Biologie des Jonctions Neuromusculaires Normales et Pathologiques ( U686 ) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
MESH: Fatigue Frizzled [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology MESH : Muscle Weakness Synaptogenesis MESH: Animals Newborn Synapse Mice [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences 0302 clinical medicine MESH: Pregnancy Pregnancy Receptors Cholinergic MESH : Female MESH: Animals Fatigue MuSK Motor Neurons 0303 health sciences Muscle Weakness synaptogenesis Hand Strength neuromuscular junction [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior MESH : Animals Newborn General Neuroscience Intracellular Signaling Peptides and Proteins Wnt signaling pathway MESH: Muscle Weakness [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences MESH: Lithium Chloride Articles Congenital myasthenic syndrome MESH : Mice Transgenic MESH : Fatigue medicine.anatomical_structure MESH: Hand Strength [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Acetylcholinesterase Female MESH: Receptor Protein-Tyrosine Kinases MESH : Mutation medicine.symptom MESH : Lithium Chloride MESH : Hand Strength MESH: Motor Neurons MESH: Myasthenic Syndromes Congenital animal structures MESH: Mutation MESH : Motor Neurons MESH: Mice Transgenic MESH : Male Primary Cell Culture MESH: Glycoproteins Mice Transgenic Biology MESH : Myasthenic Syndromes Congenital Neuromuscular junction MESH : Acetylcholinesterase [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior MESH: Primary Cell Culture 03 medical and health sciences Wnt MESH : Mice medicine Animals MESH : Primary Cell Culture MESH: Mice lithium chloride Glycoproteins 030304 developmental biology Acetylcholine receptor Myasthenic Syndromes Congenital MESH: Receptors Cholinergic Receptor Protein-Tyrosine Kinases Muscle weakness MESH : Receptor Protein-Tyrosine Kinases MESH: Acetylcholinesterase MESH : Receptors Cholinergic medicine.disease MESH : Glycoproteins MESH: Male MESH : Pregnancy Animals Newborn nervous system congenital myasthenic syndrome Mutation MESH : Neuromuscular Junction MESH : Animals MESH: Neuromuscular Junction Neuroscience MESH: Female 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuroscience Journal of Neuroscience, Society for Neuroscience, 2015, 35 (12), pp.4926-41. ⟨10.1523/JNEUROSCI.3381-14.2015⟩ Journal of Neuroscience, 2015, 35 (12), pp.4926-41. ⟨10.1523/JNEUROSCI.3381-14.2015⟩ Journal of Neuroscience, Society for Neuroscience, 2015, 35 (12), pp.4926-41. 〈10.1523/JNEUROSCI.3381-14.2015〉 |
| ISSN: | 0270-6474 1529-2401 |
| Popis: | The muscle-specific kinase MuSK is one of the key molecules orchestrating neuromuscular junction (NMJ) formation. MuSK interacts with the Wnt morphogens, through its Frizzled-like domain (cysteine-rich domain [CRD]). Dysfunction of MuSK CRD in patients has been recently associated with the onset of myasthenia, common neuromuscular disorders mainly characterized by fatigable muscle weakness. However, the physiological role of Wnt-MuSK interaction in NMJ formation and function remains to be elucidated. Here, we demonstrate that the CRD deletion of MuSK in mice caused profound defects of both muscle prepatterning, the first step of NMJ formation, and synapse differentiation associated with a drastic deficit in AChR clusters and excessive growth of motor axons that bypass AChR clusters. Moreover, adultMuSKΔCRDmice developed signs of congenital myasthenia, including severe NMJs dismantlement, muscle weakness, and fatigability. We also report, for the first time, the beneficial effects of lithium chloride, a reversible inhibitor of the glycogen synthase kinase-3, that rescued NMJ defects inMuSKΔCRDmice and therefore constitutes a novel therapeutic reagent for the treatment of neuromuscular disorders linked to Wnt-MuSK signaling pathway deficiency. Together, our data reveal that MuSK CRD is critical for NMJ formation and plays an unsuspected role in NMJ maintenance in adulthood. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|