ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Synaptic autoregulation by metalloproteases and γ-secretase.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 64 citations in OpenAlex.
- Presynaptic accumulation of APP-CTFβ may contribute to synaptic dysfunction in Alzheimer's disease.The EMBO journal · 2026Article
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Roles of Microglia in Synaptogenesis, Synaptic Pruning, and Synaptic Plasticity in Physiological Conditions and Central Nervous System Disorders.Current neuropharmacology · 2026Review
- Suppression of MT5-MMP Reveals Early Modulation of Alzheimer's Pathogenic Events in Primary Neuronal Cultures of 5xFAD Mice.Biomolecules · 2024Article
- Prenatal exposure to valproic acid reduces synaptic δ-catenin levels and disrupts ultrasonic vocalization in neonates.Neuropharmacology · 2024Article
- The autism-associated loss of δ-catenin functions disrupts social behavior.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- MT5-MMP promotes neuroinflammation, neuronal excitability and Aβ production in primary neuron/astrocyte cultures from the 5xFAD mouse model of Alzheimer's disease.Journal of neuroinflammation · 2022Article
- Quantification of the trans-synaptic partners neurexin-neuroligin in CSF of neurodegenerative diseases by parallel reaction monitoring mass spectrometry.EBioMedicine · 2022Article
- Phosphorylation of the AMPA receptor subunit GluA1 regulates clathrin-mediated receptor internalization.Journal of cell science · 2021Article
- Mice with cleavage-resistant N-cadherin exhibit synapse anomaly in the hippocampus and outperformance in spatial learning tasks.Molecular brain · 2021Article
- Microglia: sculptors of neuropathic pain?Royal Society open science · 2020Review
- RIP at the Synapse and the Role of Intracellular Domains in Neurons.Neuromolecular medicine · 2020Review
- Nrf2 activation through the PI3K/GSK-3 axis protects neuronal cells from Aβ-mediated oxidative and metabolic damage.Alzheimer's research & therapy · 2020Article
- Inhibiting pathologically active ADAM10 rescues synaptic and cognitive decline in Huntington's disease.The Journal of clinical investigation · 2019Article
- Emerging Alternative Proteinases in APP Metabolism and Alzheimer's Disease Pathogenesis: A Focus on MT1-MMP and MT5-MMP.Frontiers in aging neuroscience · 2019Review
- Shaping Synapses by the Neural Extracellular Matrix.Frontiers in neuroanatomy · 2018Review
- Lithium increases synaptic GluA2 in hippocampal neurons by elevating the δ-catenin protein.Neuropharmacology · 2017Article
- Shedding of neurexin 3β ectodomain by ADAM10 releases a soluble fragment that affects the development of newborn neurons.Scientific reports · 2016Article
- AMPAkines Target the Nucleus Accumbens to Relieve Postoperative Pain.Anesthesiology · 2016Article
- Brain region-specific effects of cGMP-dependent kinase II knockout on AMPA receptor trafficking and animal behavior.Learning & memory (Cold Spring Harbor, N.Y.) · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The proteolytic machinery comprising metalloproteases and γ-secretase, an intramembrane aspartyl protease involved in Alzheimer's disease, cleaves several substrates in addition to the extensively studied amyloid precursor protein. Some of these substrates, such as N-cadherin, are synaptic proteins involved in synapse remodeling and maintenance. Here we show, in rats and mice, that metalloproteases and γ-secretase are physiologic regulators of synapses. Both proteases are synaptic, with γ-secretase tethered at the synapse by δ-catenin, a synaptic scaffolding protein that also binds to N-cadherin and, through scaffolds, to AMPA receptor and a metalloprotease. Activity-dependent proteolysis by metalloproteases and γ-secretase takes place at both sides of the synapse, with the metalloprotease cleavage being NMDA receptor-dependent. This proteolysis decreases levels of synaptic proteins and diminishes synaptic transmission. Our results suggest that activity-dependent substrate cleavage by synaptic metalloproteases and γ-secretase modifies synaptic transmission, providing a novel form of synaptic autoregulation.
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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.