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At vertebrate neuromuscular junctions (NMJs), the synaptic basal lamina contains different extracellular matrix (ECM) proteins and synaptogenic factors that induce and maintain synaptic specializations. Here, we report that podosome-like structures (PLSs) induced by ubiquitous ECM proteins regulate the formation and remodeling of acetylcholine receptor (AChR) clusters via focal ECM degradation. Mechanistically, ECM degradation is mediated by PLS-directed trafficking and surface insertion of membrane-type 1 matrix metalloproteinase (MT1-MMP) to AChR clusters through microtubule-capturing mechanisms. Upon synaptic induction, MT1-MMP plays a crucial role in the recruitment of aneural AChR clusters for the assembly of postsynaptic specializations. Lastly, the structural defects of NMJs in embryonic MT1-MMP mice further demonstrate the physiological role of MT1-MMP in normal NMJ development. Collectively, this study suggests that postsynaptic MT1-MMP serves as a molecular switch to synaptogenesis by modulating local ECM environment for the deposition of synaptogenic signals that regulate postsynaptic differentiation at developing NMJs.
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Complement-dependent disruption of motor endplate is detected in anti-acetylcholine receptor (AChR) antibody-positive myasthenia gravis (MG). We measured serum AChR α1 subunit protein levels, which m...
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This is a phase II, single center, randomized, double-blind, placebo-controlled, study in patients with a diagnosis of anti-AchR antibody positive myasthenia gravis.
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Any autoimmune animal disease model used in the study of MYASTHENIA GRAVIS. Injection with purified neuromuscular junction acetylcholine receptor (AChR) (see RECEPTORS, CHOLINERGIC) components results in a myasthenic syndrome that has acute and chronic phases. The motor endplate pathology, loss of acetylcholine receptors, presence of circulating anti-AChR antibodies, and electrophysiologic changes make this condition virtually identical to human myasthenia gravis. Passive transfer of AChR antibodies or lymphocytes from afflicted animals to normals induces passive transfer experimental autoimmune myasthenia gravis. (From Joynt, Clinical Neurology, 1997, Ch 54, p3)
Surgical procedure by which a tendon is incised at its insertion and placed at an anatomical site distant from the original insertion. The tendon remains attached at the point of origin and takes over the function of a muscle inactivated by trauma or disease.
A protein component of the synaptic basal lamina. It has been shown to induce clustering of acetylcholine receptors on the surface of muscle fibers and other synaptic molecules in both synapse regeneration and development.