ArticleDevelopmental biology2009
Abnormal development of the neuromuscular junction in Nedd4-deficient mice.
Article in Developmental biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 79 citations in OpenAlex.
- NEDD4 promotes reactive astrogliosis by enhancing K63-linked ubiquitination and inhibiting chaperone-mediated autophagy degradation of YAP1.International journal of biological sciences · 2026Article
- 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
- Ubiquitin ligase signalling networks shape presynaptic development, function and disease.The Journal of physiology · 2025Review
- Review
- NADInternational journal of molecular sciences · 2024Article
- NEDD4-1 deficiency impairs satellite cell function during skeletal muscle regeneration.Biological research · 2023Article
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- The HECT family of E3 ubiquitin ligases and PTEN.Seminars in cancer biology · 2022Review
- Loss of NEDD4 causes complete XY gonadal sex reversal in mice.Cell death & disease · 2022Article
- HECT E3 Ubiquitin Ligase Nedd4 Is Required for Antifungal Innate Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Obestatin signalling counteracts glucocorticoid-induced skeletal muscle atrophy via NEDD4/KLF15 axis.Journal of cachexia, sarcopenia and muscle · 2021Article
- The Ubiquitinated Axon: Local Control of Axon Development and Function by Ubiquitin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Review
- The Ubiquitin Proteasome System in Neuromuscular Disorders: Moving Beyond Movement.International journal of molecular sciences · 2020Review
- Article
- The MX-Helix of Muscle nAChR Subunits Regulates Receptor Assembly and Surface Trafficking.Frontiers in molecular neuroscience · 2020Article
- Overexpression of Sirtuin 1 protein in neurons prevents and reverses experimental diabetic neuropathy.Brain : a journal of neurology · 2019Article
- Review
- Developmental biology of the meninges.Genesis (New York, N.Y. : 2000) · 2019Review
- Feedback regulation of RTK signaling in development.Developmental biology · 2019Review
- Blocking skeletal muscle DHPRs/Ryr1 prevents neuromuscular synapse loss in mutant mice deficient in type III Neuregulin 1 (CRD-Nrg1).PLoS genetics · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Nedd4 (neural precursor cell expressed developmentally down-regulated gene 4) is an E3 ubiquitin ligase highly conserved from yeast to humans. The expression of Nedd4 is developmentally down-regulated in the mammalian nervous system, but the role of Nedd4 in mammalian neural development remains poorly understood. Here we show that a null mutation of Nedd4 in mice leads to perinatal lethality: mutant mice were stillborn and many of them died in utero before birth (between E15.5-E18.5). In Nedd4 mutant embryos, skeletal muscle fiber sizes and motoneuron numbers are significantly reduced. Surviving motoneurons project axons to their target muscles on schedule, but motor nerves defasciculate upon reaching the muscle surface, suggesting that Nedd4 plays a critical role in fine-tuning the interaction between the nerve and the muscle. Electrophysiological analyses of the neuromuscular junction (NMJ) demonstrate an increased spontaneous miniature endplate potential (mEPP) frequency in Nedd4 mutants. However, the mutant neuromuscular synapses are less responsive to membrane depolarization, compared to the wildtypes. Ultrastructural analyses further reveal that the pre-synaptic nerve terminal branches at the NMJs of Nedd4 mutants are increased in number, but decreased in diameter compared to the wildtypes. These ultrastructural changes are consistent with functional alternation of the NMJs in Nedd4 mutants. Unexpectedly, Nedd4 is not expressed in motoneurons, but is highly expressed in skeletal muscles and Schwann cells. Together, these results demonstrate that Nedd4 is involved in regulating the formation and function of the NMJs through non-cell autonomous mechanisms.
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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.