Evidence map›Paper›PMID 18337251›Full record

ArticleThe Journal of biological chemistry2008

Activated nuclear metabotropic glutamate receptor mGlu5 couples to nuclear Gq/11 proteins to generate inositol 1,4,5-trisphosphate-mediated nuclear Ca2+ release.

Vikas Kumar, Yuh-Jiin I Jong, Karen L O'Malley

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

50 citing papers in PubMed, 95 citations in OpenAlex.

  1. Article
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  4. Mechanisms of Location Bias in G Protein-Coupled Receptors.Handbook of experimental pharmacology · 2026
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  10. Altered Expression andCurrent neuropharmacology · 2022
    Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. The Emerging Role of Adhesion GPCRs in Cancer.ACS pharmacology & translational science · 2020
    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

3 authors at 1 institution in 1 country.

Vikas KumarDepartment of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Yuh-Jiin I Jong
Karen L O'Malley
Washington University in St. Louis · US

Funding

Washington University Center for Translational NeuroscienceP30NS057105 · NINDS · WASHINGTON UNIVERSITY · PI HOLTZMAN, DAVID M. · 2006 to 2011
$8.7M
METABOTROPIC RECEPTORS--STRUCTURE, FUNCTION, REGULATIONR01MH057817 · NIMH · WASHINGTON UNIVERSITY · PI O'MALLEY, KAREN L · 1998 to 2006
$2.1M
Signaling By Nuclear G-Protein Coupled ReceptorsR21MH069646 · NIMH · WASHINGTON UNIVERSITY · PI O'MALLEY, KAREN L · 2004 to 2005
$275k
NIMH NIH HHS MH57817NIMH NIH HHS MH69646NINDS NIH HHS NS057105
6 · The paper itself

Abstract

Recently we have shown that the metabotropic glutamate 5 (mGlu5) receptor can be expressed on nuclear membranes of heterologous cells or endogenously on striatal neurons where it can mediate nuclear Ca2+ changes. Here, pharmacological, optical, and genetic techniques were used to show that upon activation, nuclear mGlu5 receptors generate nuclear inositol 1,4,5-trisphosphate (IP3) in situ. Specifically, expression of an mGlu5 F767S mutant in HEK293 cells that blocks Gq/11 coupling or introduction of a dominant negative Galphaq construct in striatal neurons prevented nuclear Ca2+ changes following receptor activation. These data indicate that nuclear mGlu5 receptors couple to Gq/11 to mobilize nuclear Ca2+. Nuclear mGlu5-mediated Ca2+ responses could also be blocked by the phospholipase C (PLC) inhibitor, U73122, the phosphatidylinositol (PI) PLC inhibitor 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine (ET-18-OCH3), or by using small interfering RNA targeted against PLCbeta1 demonstrating that PI-PLC is involved. Direct assessment of inositol phosphate production using a PIP2/IP3 "biosensor" revealed for the first time that IP3 can be generated in the nucleus following activation of nuclear mGlu5 receptors. Finally, both IP3 and ryanodine receptor blockers prevented nuclear mGlu5-mediated increases in intranuclear Ca2+. Collectively, this study shows that like plasma membrane receptors, activated nuclear mGlu5 receptors couple to Gq/11 and PLC to generate IP3-mediated release of Ca2+ from Ca2+-release channels in the nucleus. Thus the nucleus can function as an autonomous organelle independent of signals originating in the cytoplasm, and nuclear mGlu5 receptors play a dynamic role in mobilizing Ca2+ in a specific, localized fashion.

Indexed as

Biosensing TechniquesCalciumCell LineCell NucleusEnzyme InhibitorsEstrenesGenes, DominantGTP-Binding Protein alpha Subunits, Gq-G11HumansInositol 1,4,5-TrisphosphateMicroscopy, FluorescenceModels, BiologicalNuclear EnvelopePyrrolidinonesType C Phospholipases1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dioneCalciumEnzyme InhibitorsEstrenesGTP-Binding Protein alpha Subunits, Gq-G11Inositol 1,4,5-TrisphosphatePyrrolidinonesType C Phospholipases

Identifiers

PMID18337251
PMCPMC2376237
OpenAlexW1994363140

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.