Evidence map›Paper›PMID 22179603›Full record

ArticleThe Journal of biological chemistry2012

N-methyl-D-aspartate receptor mechanosensitivity is governed by C terminus of NR2B subunit.

Pallab Singh, Shachee Doshi, Jennifer M Spaethling, Adam J Hockenberry, Tapan P Patel, Donna M Geddes-Klein, David R Lynch, David F Meaney

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 15% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Membrane Stretch Gates NMDA Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022
    Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Regional NeurodegenerationFrontiers in computational neuroscience · 2021
    Article
  16. Review
  17. Remembering Mechanosensitivity of NMDA Receptors.Frontiers in cellular neuroscience · 2019
    Review
  18. Review
  19. Article
  20. Review
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 2 institutions in 1 country.

Pallab SinghDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Shachee Doshi
Jennifer M Spaethling
Adam J Hockenberry
Tapan P Patel
Donna M Geddes-Klein
David R Lynch
David F Meaney
University of Pennsylvania · USChildren's Hospital of Philadelphia · US

Funding

Force Transmission in the Central Nervous SystemR01HD041699 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI MEANEY, DAVID F · 2001 to 2011
$6.3M
BIOMECHANICAL ANALYSIS OF TRAUMATIC BRAIN INJURY MODELSR01NS035712 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI MEANEY, DAVID F · 1997 to 2010
$2.9M
CONTROL OF NEURONAL FIRING BY ADAPTATIONR01NS015212 · NINDS · DUKE UNIVERSITY · PI WILSON, WILKIE A · 1985 to 1985
–
NICHD NIH HHS HD41699NICHD NIH HHS R01 HD041699NINDS NIH HHS NS015212NINDS NIH HHS NS35712NINDS NIH HHS R01 NS035712
6 · The paper itself

Abstract

N-methyl-D-aspartate receptors (NMDARs), critical mediators of both physiologic and pathologic neurological signaling, have previously been shown to be sensitive to mechanical stretch through the loss of its native Mg(2+) block. However, the regulation of this mechanosensitivity has yet to be further explored. Furthermore, as it has become apparent that NMDAR-mediated signaling is dependent on specific NMDAR subtypes, as governed by the identity of the NR2 subunit, a crucial unanswered question is the role of subunit composition in observed NMDAR mechanosensitivity. Here, we used a recombinant system to assess the mechanosensitivity of specific subtypes and demonstrate that the mechanosensitive property is uniquely governed by the NR2B subunit. NR1/NR2B NMDARs displayed significant stretch sensitivity, whereas NR1/NR2A NMDARs did not respond to stretch. Furthermore, NR2B mechanosensitivity was regulated by PKC activity, because PKC inhibition reduced stretch responses in transfected HEK 293 cells and primary cortical neurons. Finally, using NR2B point mutations, we identified a PKC phosphorylation site, Ser-1323 on NR2B, as a unique critical regulator of stretch sensitivity. These data suggest that the selective mechanosensitivity of NR2B can significantly impact neuronal response to traumatic brain injury and illustrate that the mechanical tone of the neuron can be dynamically regulated by PKC activity.

Indexed as

Mechanotransduction, CellularAnimalsBrain InjuriesHEK293 CellsHumansNeuronsPoint MutationProtein Kinase CRatsReceptors, N-Methyl-D-AspartateTransfectionNR2B NMDA receptorProtein Kinase CReceptors, N-Methyl-D-Aspartate

Identifiers

PMID22179603
PMCPMC3281702
OpenAlexW2066754391

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.