ArticleNature neuroscience2011
APC(Cdh1) mediates EphA4-dependent downregulation of AMPA receptors in homeostatic plasticity.
Article in Nature neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 178 citations in OpenAlex.
- Convergence and divergence of molecular mechanisms in Hebbian and homeostatic plasticity.Frontiers in synaptic neuroscience · 2026Review
- Comparative Single-Cell Transcriptome Analysis of c-Met Receptor Expressing and Non-Expressing Projection Neurons in the Developing Frontal and Visual Cortices.Developmental neuroscience · 2025Article
- DEPDC5 regulates the strength of excitatory synaptic transmission by interacting with ubiquitin-specific protease 46.Neurobiology of disease · 2025Article
- UBR-1 enzyme network regulates glutamate homeostasis to affect organismal behavior and developmental viability.bioRxiv : the preprint server for biology · 2025Article
- Cullin-RING Ubiquitin Ligases in Neurodevelopment and Neurodevelopmental Disorders.Biomedicines · 2025Review
- Astrocytic EphA4 signaling is important for the elimination of excitatory synapses in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- VCP controls KCC2 degradation through FAF1 recruitment and accelerates emergence from anesthesia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Understanding neurodevelopmental proteasomopathies as new rare disease entities: A review of current concepts, molecular biomarkers, and perspectives.Genes & diseases · 2024Review
- Multiomics of early epileptogenesis in mice reveals phosphorylation and dephosphorylation-directed growth and synaptic weakening.iScience · 2024Article
- Identification of secretory autophagy as a mechanism modulating activity-induced synaptic remodeling.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Molecular Mechanisms of AMPA Receptor Trafficking in the Nervous System.International journal of molecular sciences · 2023Review
- Article
- Schizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids.Nature communications · 2023Article
- Early alterations in the MCH system link aberrant neuronal activity and sleep disturbances in a mouse model of Alzheimer's disease.Nature neuroscience · 2023Article
- Emergence of consciousness from anesthesia through ubiquitin degradation of KCC2 in the ventral posteromedial nucleus of the thalamus.Nature neuroscience · 2023Article
- RNF220 is an E3 ubiquitin ligase for AMPA receptors to regulate synaptic transmission.Science advances · 2022Article
- Selective endocytosis of CaScience advances · 2022Article
- Instructive roles of astrocytes in hippocampal synaptic plasticity: neuronal activity-dependent regulatory mechanisms.The FEBS journal · 2022Review
- APC/C-Cdh1-targeted substrates as potential therapies for Alzheimer's disease.Frontiers in pharmacology · 2022Review
- Article
49 more citing papers are in PubMed but not listed here.
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8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Homeostatic plasticity is crucial for maintaining neuronal output by counteracting unrestrained changes in synaptic strength. Chronic elevation of synaptic activity by bicuculline reduces the amplitude of miniature excitatory postsynaptic currents (mEPSCs), but the underlying mechanisms of this effect remain unclear. We found that activation of EphA4 resulted in a decrease in synaptic and surface GluR1 and attenuated mEPSC amplitude through a degradation pathway that requires the ubiquitin proteasome system (UPS). Elevated synaptic activity resulted in increased tyrosine phosphorylation of EphA4, which associated with the ubiquitin ligase anaphase-promoting complex (APC) and its activator Cdh1 in neurons in a ligand-dependent manner. APC(Cdh1) interacted with and targeted GluR1 for proteasomal degradation in vitro, whereas depletion of Cdh1 in neurons abolished the EphA4-dependent downregulation of GluR1. Knockdown of EphA4 or Cdh1 prevented the reduction in mEPSC amplitude in neurons that was a result of chronic elevated activity. Our results define a mechanism by which EphA4 regulates homeostatic plasticity through an APC(Cdh1)-dependent degradation pathway.
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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.