ArticleProceedings of the National Academy of Sciences of the United States of America2022
MDGA1 negatively regulates amyloid precursor protein-mediated synapse inhibition in the hippocampus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. 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 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Cell-to-cell variability and gain of methylation at polycomb CpG islands as a hallmark of aging.Nature communications · 2026Article
- Neurexins, Ephrin receptors, and N-cadherin signaling as emerging mechanisms in synaptic dysfunction and neurodegenerative diseases.Communications biology · 2026Review
- Bazedoxifene reverses sexually dimorphic autistic-like abnormalities in biallelic MDGA1-mutant mice.EMBO molecular medicine · 2026Article
- Localization and Functional Characterization of MDGA1 in Mouse Hippocampus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Paralogs of Slitrk cell adhesion molecules configure excitatory synapse specificity via distinct cellular mechanisms.PLoS biology · 2025Article
- Telomeric DNA damage response mediates neurotoxicity of Aβ42 oligomers in Alzheimer's disease.The EMBO journal · 2025Article
- Article
- EphB2 receptor tyrosine kinase-mediated excitatory synaptic functions are negatively modulated by MDGA2.Progress in neurobiology · 2025Article
- Functional Neuroligin-2-MDGA1 interactions differentially regulate synaptic GABACommunications biology · 2024Article
- Impaired Hippocampal Long-Term Potentiation and Memory Deficits upon Haploinsufficiency of MDGA1 Can Be Rescued by Acute Administration of D-Cycloserine.International journal of molecular sciences · 2024Article
- MDGA2 Constrains Glutamatergic Inputs Selectively onto CA1 Pyramidal Neurons to Optimize Neural Circuits for Plasticity, Memory, and Social Behavior.Neuroscience bulletin · 2024Article
- MDGAs perform activity-dependent synapse type-specific suppression via distinct extracellular mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Upregulation of Spinal MDGA1 in Rats After Nerve Injury Alters Interactions Between Neuroligin-2 and Postsynaptic Scaffolding Proteins and Increases GluR1 Subunit Surface Delivery in the Spinal Cord Dorsal Horn.Neurochemical research · 2024Article
- standR: spatial transcriptomic analysis for GeoMx DSP data.Nucleic acids research · 2024Article
- Dual-specificity protein phosphatase 6 (DUSP6) overexpression reduces amyloid load and improves memory deficits in male 5xFAD mice.Frontiers in aging neuroscience · 2024Article
- Plasma levels of neurology-related proteins are associated with cognitive performance in an older population with overweight/obesity and metabolic syndrome.GeroScience · 2023Article
- LPS induces microglial activation and GABAergic synaptic deficits in the hippocampus accompanied by prolonged cognitive impairment.Scientific reports · 2023Article
- Designer molecules of the synaptic organizer MDGA1 reveal 3D conformational control of biological function.The Journal of biological chemistry · 2023Article
- Identification of the diagnostic genes and immune cell infiltration characteristics of gastric cancer using bioinformatics analysis and machine learning.Frontiers in genetics · 2022Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Balanced synaptic inhibition, controlled by multiple synaptic adhesion proteins, is critical for proper brain function. MDGA1 (meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu [MAM] domain-containing glycosylphosphatidylinositol anchor protein 1) suppresses synaptic inhibition in mammalian neurons, yet the molecular mechanisms underlying MDGA1-mediated negative regulation of GABAergic synapses remain unresolved. Here, we show that the MDGA1 MAM domain directly interacts with the extension domain of amyloid precursor protein (APP). Strikingly, MDGA1-mediated synaptic disinhibition requires the MDGA1 MAM domain and is prominent at distal dendrites of hippocampal CA1 pyramidal neurons. Down-regulation of APP in presynaptic GABAergic interneurons specifically suppressed GABAergic, but not glutamatergic, synaptic transmission strength and inputs onto both the somatic and dendritic compartments of hippocampal CA1 pyramidal neurons. Moreover, APP deletion manifested differential effects in somatostatin- and parvalbumin-positive interneurons in the hippocampal CA1, resulting in distinct alterations in inhibitory synapse numbers, transmission, and excitability. The infusion of MDGA1 MAM protein mimicked postsynaptic MDGA1 gain-of-function phenotypes that involve the presence of presynaptic APP. The overexpression of MDGA1 wild type or MAM, but not MAM-deleted MDGA1, in the hippocampal CA1 impaired novel object-recognition memory in mice. Thus, our results establish unique roles of APP-MDGA1 complexes in hippocampal neural circuits, providing unprecedented insight into
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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.