ArticleNeuroscience2009
Rapsyn interacts with the muscle acetylcholine receptor via alpha-helical domains in the alpha, beta, and epsilon subunit intracellular loops.
Article in Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- Protein networking: nicotinic acetylcholine receptors and their protein-protein-associations.Molecular and cellular biochemistry · 2024Review
- Targeted degradation of oncogenic BCR-ABL by silencing the gene of NEDD8 E3 ligase RAPSYN.Journal of nanobiotechnology · 2024Article
- A clinical perspective on muscle specific kinase antibody positive myasthenia gravis.Frontiers in immunology · 2024Review
- The role of Rapsyn in neuromuscular junction and congenital myasthenic syndrome.Biomolecules & biomedicine · 2023Review
- Myosin Va: Capturing cAMP for synaptic plasticity.Frontiers in physiology · 2023Review
- Neuromuscular Junction Dysfunction in Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2022Review
- Membraneless condensates by Rapsn phase separation as a platform for neuromuscular junction formation.Neuron · 2021Article
- An Inside Job: Molecular Determinants for Postsynaptic Localization of Nicotinic Acetylcholine Receptors.Molecules (Basel, Switzerland) · 2021Review
- The Neuromuscular Junction in Health and Disease: Molecular Mechanisms Governing Synaptic Formation and Homeostasis.Frontiers in molecular neuroscience · 2020Review
- Myasthenia Gravis: From the Viewpoint of Pathogenicity Focusing on Acetylcholine Receptor Clustering, Trans-Synaptic Homeostasis and Synaptic Stability.Frontiers in molecular neuroscience · 2020Article
- Impairment Mechanisms and Intervention Approaches for Aged Human Neuromuscular Junctions.Frontiers in molecular neuroscience · 2020Review
- A mechanism in agrin signaling revealed by a prevalent Rapsyn mutation in congenital myasthenic syndrome.eLife · 2019Article
- Vezatin is required for the maturation of the neuromuscular synapse.Molecular biology of the cell · 2019Article
- Muscle-Specific Tyrosine Kinase and Myasthenia Gravis Owing to Other Antibodies.Neurologic clinics · 2018Review
- Article
- Dynein disruption perturbs post-synaptic components and contributes to impaired MuSK clustering at the NMJ: implication in ALS.Scientific reports · 2016Article
- AChRs Are Essential for the Targeting of Rapsyn to the Postsynaptic Membrane of NMJs in Living Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Neuromuscular Junction Impairment in Amyotrophic Lateral Sclerosis: Reassessing the Role of Acetylcholinesterase.Frontiers in molecular neuroscience · 2016Review
- Zebrafish mutants of the neuromuscular junction: swimming in the gene pool.The journal of physiological sciences : JPS · 2015Review
- Muscle-specific kinase (MuSK) autoantibodies suppress the MuSK pathway and ACh receptor retention at the mouse neuromuscular junction.The Journal of physiology · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
At the developing vertebrate neuromuscular junction, the acetylcholine receptor becomes aggregated at high density in the postsynaptic muscle membrane. Receptor localization is regulated by the motoneuron-derived factor, agrin, and requires an intracellular, scaffolding protein called rapsyn. However, it remains unclear where rapsyn binds on the acetylcholine receptor and how their interaction is regulated. In this study, we identified rapsyn's binding site on the acetylcholine receptor using chimeric constructs where the intracellular domain of CD4 was substituted for the major intracellular loop of each mouse acetylcholine receptor subunit. When expressed in heterologous cells, we found that rapsyn clustered and cytoskeletally anchored CD4-alpha, beta and epsilon subunit loops but not CD4-delta loop. Rapsyn-mediated clustering and anchoring was highest for beta loop, followed by epsilon and alpha, suggesting that rapsyn interacts with the loops with different affinities. Moreover, by making deletions within the beta subunit intracellular loop, we show that rapsyn interacts with the alpha-helical region, a secondary structural motif present in the carboxyl terminal portion of the subunit loops. When expressed in muscle cells, rapsyn co-immunoprecipitated together with a CD4-alpha helical region chimera, independent of agrin signaling. Together, these findings demonstrate that rapsyn interacts with the acetylcholine receptor via an alpha-helical structural motif conserved between the alpha, beta and epsilon subunits. Binding at this site likely mediates the critical rapsyn interaction involved in localizing the acetylcholine receptor at the neuromuscular junction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.