ArticleeLife2013
APP interacts with LRP4 and agrin to coordinate the development of the neuromuscular junction in mice.
Article in eLife, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 71 citations in OpenAlex.
- Bltp1 Is Required for Survival and Normal Development and Function of the Neuromuscular Junction in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Effects and mechanisms of APP and its cleavage product Aβ in the comorbidity of sarcopenia and Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
- Amyloid precursor protein and its interacting proteins in neurodevelopment.Biochemical Society transactions · 2023Review
- APP in the Neuromuscular Junction for the Development of Sarcopenia and Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Intrafusal-fiber LRP4 for muscle spindle formation and maintenance in adult and aged animals.Nature communications · 2023Article
- Balancing WNT signalling in early forebrain development: The role of LRP4 as a modulator of LRP6 function.Frontiers in cell and developmental biology · 2023Article
- NMJ-related diseases beyond the congenital myasthenic syndromes.Frontiers in cell and developmental biology · 2023Review
- Age Related Changes in Muscle Mass and Force Generation in the Triple Transgenic (3xTgAD) Mouse Model of Alzheimer's Disease.Frontiers in aging neuroscience · 2022Article
- Synapse-specific Lrp4 mRNA enrichment requires Lrp4/MuSK signaling, muscle activity and Wnt non-canonical pathway.Cell & bioscience · 2021Article
- Conservation and Innovation: Versatile Roles for LRP4 in Nervous System Development.Journal of developmental biology · 2021Review
- Secreted Signaling Molecules at the Neuromuscular Junction in Physiology and Pathology.International journal of molecular sciences · 2021Review
- APP Binds to the EGFR Ligands HB-EGF and EGF, Acting Synergistically with EGF to Promote ERK Signaling and Neuritogenesis.Molecular neurobiology · 2021Article
- Lipin 1 deficiency causes adult-onset myasthenia with motor neuron dysfunction in humans and neuromuscular junction defects in zebrafish.Theranostics · 2021Article
- How to Build and to Protect the Neuromuscular Junction: The Role of the Glial Cell Line-Derived Neurotrophic Factor.International journal of molecular sciences · 2020Review
- LRP4 LDLα repeats of astrocyte enhance dendrite arborization of the neuron.Molecular brain · 2020Article
- CTGF/CCN2 facilitates LRP4-mediated formation of the embryonic neuromuscular junction.EMBO reports · 2020Article
- Spatiotemporal Distribution of Agrin after Intrathecal Injection and Its Protective Role in Cerebral Ischemia/Reperfusion Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Myasthenia Gravis: From the Viewpoint of Pathogenicity Focusing on Acetylcholine Receptor Clustering, Trans-Synaptic Homeostasis and Synaptic Stability.Frontiers in molecular neuroscience · 2020Article
- Skeletal muscle: A review of molecular structure and function, in health and disease.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Nerve, Muscle, and Synaptogenesis.Cells · 2019Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
ApoE, ApoE receptors and APP cooperate in the pathogenesis of Alzheimer's disease. Intriguingly, the ApoE receptor LRP4 and APP are also required for normal formation and function of the neuromuscular junction (NMJ). In this study, we show that APP interacts with LRP4, an obligate co-receptor for muscle-specific tyrosine kinase (MuSK). Agrin, a ligand for LRP4, also binds to APP and co-operatively enhances the interaction of APP with LRP4. In cultured myotubes, APP synergistically increases agrin-induced acetylcholine receptor (AChR) clustering. Deletion of the transmembrane domain of LRP4 (LRP4 ECD) results in growth retardation of the NMJ, and these defects are markedly enhanced in APP(-/-);LRP4(ECD/ECD) mice. Double mutant NMJs are significantly reduced in size and number, resulting in perinatal lethality. Our findings reveal novel roles for APP in regulating neuromuscular synapse formation through hetero-oligomeric interaction with LRP4 and agrin and thereby provide new insights into the molecular mechanisms that govern NMJ formation and maintenance. DOI:http://dx.doi.org/10.7554/eLife.00220.001.
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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.