Evidence map›Paper›PMID 26604311›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

PSD-95 family MAGUKs are essential for anchoring AMPA and NMDA receptor complexes at the postsynaptic density.

Xiaobing Chen, Jonathan M Levy, Austin Hou, Christine Winters, Rita Azzam, Alioscka A Sousa, Richard D Leapman, Roger A Nicoll, Thomas S Reese

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers.

0numbers the graph read from it
0cells of the map it votes in
180citing papers in PubMed
8.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

180 citing papers in PubMed, 308 citations in OpenAlex.

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  16. Nonionic signaling rapidly remodels postsynaptic DLG to induce retrograde homeostatic plasticity.Proceedings of the National Academy of Sciences of the United States of America · 2025
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120 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Xiaobing ChenLaboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892;
Jonathan M LevyDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158;
Austin HouLaboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892;
Christine WintersLaboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892;
Rita AzzamLaboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892;
Alioscka A SousaLaboratory of Cellular Imaging and Macromolecular Biophysics, National Institutes of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892.
Richard D LeapmanLaboratory of Cellular Imaging and Macromolecular Biophysics, National Institutes of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892.
Roger A NicollDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158;
Thomas S ReeseLaboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892; treese@mbl.edu.
National Institute of Neurological Disorders and Stroke · USNational Institutes of Health · USUniversity of California, San Francisco · USNational Institute of Biomedical Imaging and Bioengineering · US

Funding

NEUROTRANSMITTER EFFECTS ON LOCAL NEURONAL CIRCUITSR37MH038256 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NICOLL, ROGER A · 1987 to 2016
$9.0M
Electron Tomography Of Cellular StructuresZIAEB000017 · NIBIB · NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING · PI LEAPMAN, RICHARD · 2009 to 2016
$838k
Intramural NIH HHSNIMH NIH HHS R37 MH038256
6 · The paper itself

Abstract

The postsynaptic density (PSD)-95 family of membrane-associated guanylate kinases (MAGUKs) are major scaffolding proteins at the PSD in glutamatergic excitatory synapses, where they maintain and modulate synaptic strength. How MAGUKs underlie synaptic strength at the molecular level is still not well understood. Here, we explore the structural and functional roles of MAGUKs at hippocampal excitatory synapses by simultaneous knocking down PSD-95, PSD-93, and synapse-associated protein (SAP)102 and combining electrophysiology and transmission electron microscopic (TEM) tomography imaging to analyze the resulting changes. Acute MAGUK knockdown greatly reduces synaptic transmission mediated by α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) and N-methyl-d-aspartate receptors (NMDARs). This knockdown leads to a significant rise in the number of silent synapses, diminishes the size of PSDs without changes in pre- or postsynaptic membrane, and depletes the number of membrane-associated PSD-95-like vertical filaments and transmembrane structures, identified as AMPARs and NMDARs by EM tomography. The differential distribution of these receptor-like structures and dependence of their abundance on PSD size matches that of AMPARs and NMDARs in the hippocampal synapses. The loss of these structures following MAGUK knockdown tracks the reduction in postsynaptic AMPAR and NMDAR transmission, confirming the structural identities of these two types of receptors. These results demonstrate that MAGUKs are required for anchoring both types of glutamate receptors at the PSD and are consistent with a structural model where MAGUKs, corresponding to membrane-associated vertical filaments, are the essential structural proteins that anchor and organize both types of glutamate receptors and govern the overall molecular organization of the PSD.

Indexed as

AnimalsCells, CulturedDisks Large Homolog 4 ProteinGene Knockdown TechniquesIntracellular Signaling Peptides and ProteinsMembrane ProteinsPost-Synaptic DensityRatsReceptors, AMPAReceptors, N-Methyl-D-AspartateDisks Large Homolog 4 ProteinDlg4 protein, ratIntracellular Signaling Peptides and ProteinsMembrane ProteinsReceptors, AMPAReceptors, N-Methyl-D-AspartateAMPAREM tomographyknockdownMAGUKsNMDAR

Identifiers

PMID26604311
PMCPMC4687590
OpenAlexW2178843014

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.