ArticleNature medicine2013
Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down's syndrome.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 1 of them a synthesis that pooled it.
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Who cites it
158 citing papers in PubMed, 1 synthesis or guideline pooled it, 262 citations in OpenAlex.
- Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype.Human molecular genetics · 2016Pooled it
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Novel Variants Identified in Families With SNX27 -Related Neurodevelopmental Disorder, Aiding in Characterizing Its Genotypic and Phenotypic Spectrum.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2026Article
- Linear ubiquitination of the NMDA receptor GluN2A subunit facilitates the GluN2B-to-GluN2A switch and synaptic maturation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- SNX6-mediated subunit-specific secretory trafficking of AMPA receptors regulates synaptic function and plasticity.Communications biology · 2025Article
- Dual endomembrane recycling pathways function in parallel to support synapse maintenance and plasticity.Neuroscience · 2025Article
- Uric Acid Functions as an Endogenous Modulator of Microglial Function and Amyloid Clearance in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PI(3)P coordinates SNX17- and SNX27-dependent protein recycling for long-term synaptic plasticity.The Journal of cell biology · 2025Article
- Synaptojanin-1 supports VPS35-dependent trafficking of dopamine D2 autoreceptors at presynaptic terminals.Research square · 2025Article
- The schizophrenia risk gene C4 induces pathological synaptic loss by impairing AMPAR trafficking.Molecular psychiatry · 2025Article
- Endosomal traffic disorders: a driving force behind neurodegenerative diseases.Translational neurodegeneration · 2024Review
- Metabolic reprogramming in astrocytes results in neuronal dysfunction in intellectual disability.Molecular psychiatry · 2024Article
- Menin Deficiency Induces Autism-Like Behaviors by Regulating Foxg1 Transcription and Participates in Foxg1-Related Encephalopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- SNX27: A trans-species cognitive modulator with implications for anxiety and stress susceptibility.Neurobiology of stress · 2024Article
- SNX17 Mediates Dendritic Spine Maturation via p140Cap.Molecular neurobiology · 2024Article
- Transcriptome- and proteome-wide effects of a circular RNA encompassing four early exons of the spinal muscular atrophy genes.Research square · 2024Article
- Increased burden of rare protein-truncating variants in constrained, brain-specific and synaptic genes in extremely impulsively violent males with antisocial personality disorder.Genes, brain, and behavior · 2024Article
- Partial loss of Sorting Nexin 27 resembles age- and Down syndrome-associated T cell dysfunctions.Immunity & ageing : I & A · 2024Article
- Direct modulation of G protein-gated inwardly rectifying potassium (GIRK) channels.Frontiers in physiology · 2024Review
- Understanding the genetic mechanisms and cognitive impairments in Down syndrome: towards a holistic approach.Journal of neurology · 2024Review
98 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
Sorting nexin 27 (SNX27), a brain-enriched PDZ domain protein, regulates endocytic sorting and trafficking. Here we show that Snx27(-/-) mice have severe neuronal deficits in the hippocampus and cortex. Although Snx27(+/-) mice have grossly normal neuroanatomy, we found defects in synaptic function, learning and memory and a reduction in the amounts of ionotropic glutamate receptors (NMDA and AMPA receptors) in these mice. SNX27 interacts with these receptors through its PDZ domain, regulating their recycling to the plasma membrane. We demonstrate a concomitant reduced expression of SNX27 and CCAAT/enhancer binding protein β (C/EBPβ) in Down's syndrome brains and identify C/EBPβ as a transcription factor for SNX27. Down's syndrome causes overexpression of miR-155, a chromosome 21-encoded microRNA that negatively regulates C/EBPβ, thereby reducing SNX27 expression and resulting in synaptic dysfunction. Upregulating SNX27 in the hippocampus of Down's syndrome mice rescues synaptic and cognitive deficits. Our identification of the role of SNX27 in synaptic function establishes a new molecular mechanism of Down's syndrome pathogenesis.
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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.