Evidence map›Paper›PMID 29656875›Full record

ArticleNeuron2018

Structural Mechanism of Functional Modulation by Gene Splicing in NMDA Receptors.

Michael C Regan, Timothy Grant, Miranda J McDaniel, Erkan Karakas, Jing Zhang, Stephen F Traynelis, Nikolaus Grigorieff, Hiro Furukawa

Open access · bronzeAbstract read
In one paragraph

Article in Neuron, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

47 citing papers in PubMed, 77 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Src dependency of the regulation of LTP by alternative splicing ofPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Article
  11. Article
  12. Article
  13. Article
  14. Structural insights into NMDA receptor pharmacology.Biochemical Society transactions · 2023
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
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

8 authors at 4 institutions in 1 country.

Michael C ReganWM Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Timothy GrantJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
Miranda J McDanielDepartment of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Erkan KarakasDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Jing ZhangDepartment of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Stephen F TraynelisDepartment of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Nikolaus GrigorieffJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
Hiro FurukawaWM Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. Electronic address: furukawa@cshl.edu.
Emory University · USCold Spring Harbor Laboratory · USHoward Hughes Medical Institute · USVanderbilt University · US

Funding

Structures and reagents of NMDA receptorsR01MH085926 · NIMH · COLD SPRING HARBOR LABORATORY · PI Hiroyasu Furukawa · 2010 to 2026
$8.9M
Graduate Training in the Pharmacological StudiesT32GM008602 · NIGMS · EMORY UNIVERSITY · PI HALL, RANDY A. · 1996 to 2021
$5.1M
Control of Glutamate Receptor FunctionR01NS036654 · NINDS · EMORY UNIVERSITY · PI TRAYNELIS, STEPHEN F · 1998 to 2018
$3.7M
Control of glutamate receptor functionR37NS036654 · NINDS · EMORY UNIVERSITY · PI TRAYNELIS, STEPHEN F · 2007 to 2013
$2.4M
STRUCTURE AND FUNCTION OF HETERO-MULTIMERIC GLUTAMATE RECEPTORSR01GM105730 · NIGMS · COLD SPRING HARBOR LABORATORY · PI FURUKAWA, HIROYASU · 2014 to 2017
$2.0M
Structural Basis of Allosteric Regulation in the NMDA ReceptorF32NS093753 · NINDS · COLD SPRING HARBOR LABORATORY · PI REGAN, MICHAEL CASEY · 2015 to 2018
$167k
NIGMS NIH HHS R01 GM105730NIGMS NIH HHS T32 GM008602NIMH NIH HHS R01 MH085926NINDS NIH HHS F32 NS093753NINDS NIH HHS R01 NS036654NINDS NIH HHS R37 NS036654
6 · The paper itself

Abstract

Alternative gene splicing gives rise to N-methyl-D-aspartate (NMDA) receptor ion channels with defined functional properties and unique contributions to calcium signaling in a given chemical environment in the mammalian brain. Splice variants possessing the exon-5-encoded motif at the amino-terminal domain (ATD) of the GluN1 subunit are known to display robustly altered deactivation rates and pH sensitivity, but the underlying mechanism for this functional modification is largely unknown. Here, we show through cryoelectron microscopy (cryo-EM) that the presence of the exon 5 motif in GluN1 alters the local architecture of heterotetrameric GluN1-GluN2 NMDA receptors and creates contacts with the ligand-binding domains (LBDs) of the GluN1 and GluN2 subunits, which are absent in NMDA receptors lacking the exon 5 motif. The unique interactions established by the exon 5 motif are essential to the stability of the ATD/LBD and LBD/LBD interfaces that are critically involved in controlling proton sensitivity and deactivation.

Indexed as

AnimalsCell LineFemaleHEK293 CellsHumansInsectaProtein SplicingProtein Structure, SecondaryProtein Structure, TertiaryReceptors, N-Methyl-D-AspartateXenopus laevisReceptors, N-Methyl-D-Aspartatealternative splicingcryo-EMelectrophysiologyNMDA receptor

Identifiers

PMID29656875
PMCPMC5963293
OpenAlexW2796905767

What OpenQuestion holds

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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.