Evidence map›Paper›PMID 23166501›Full record

ArticlePLoS pathogens2012

Heterotrimeric G-protein signaling is critical to pathogenic processes in Entamoeba histolytica.

Dustin E Bosch, Adam J Kimple, Robin E Muller, Patrick M Giguère, Mischa Machius, Francis S Willard, Brenda R S Temple, David P Siderovski

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Acetylcholine UpregulatesFrontiers in cellular and infection microbiology · 2020
    Article
  5. Uncovering the Cyclic AMP Signaling Pathway of the Protozoan ParasiteFrontiers in cellular and infection microbiology · 2020
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Regulation of virulence of Entamoeba histolytica.Annual review of microbiology · 2014
    Review
  11. Article
  12. G protein signaling in the parasite Entamoeba histolytica.Experimental & molecular medicine · 2013
    Review
  13. 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 2 institutions in 1 country.

Dustin E BoschDepartment of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Adam J Kimple
Robin E Muller
Patrick M Giguère
Mischa Machius
Francis S Willard
Brenda R S Temple
David P Siderovski
University of North Carolina at Chapel Hill · USWest Virginia University · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Structural Determinants of Heterotrimeric G-protein Nucleotide CyclingR01GM082892 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SIDEROVSKI, DAVID P. · 2008 to 2011
$924k
Towards small molecule modulators of RGS proteinsF30MH074266 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KIMPLE, ADAM J · 2006 to 2011
$162k
Elucidating a G-protein signaling pathway in E. histolytica amoebic colitisF30DK091978 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOSCH, DUSTIN E · 2011 to 2013
$105k
NCI NIH HHS P30 CA016086NIDDK NIH HHS DK091978NIDDK NIH HHS F30 DK091978NIGMS NIH HHS GM082892NIGMS NIH HHS R01 GM082892NIMH NIH HHS F30 MH074266NIMH NIH HHS MH074266
6 · The paper itself

Abstract

Heterotrimeric G-protein signaling pathways are vital components of physiology, and many are amenable to pharmacologic manipulation. Here, we identify functional heterotrimeric G-protein subunits in Entamoeba histolytica, the causative agent of amoebic colitis. The E. histolytica Gα subunit EhGα1 exhibits conventional nucleotide cycling properties and is seen to interact with EhGβγ dimers and a candidate effector, EhRGS-RhoGEF, in typical, nucleotide-state-selective fashions. In contrast, a crystal structure of EhGα1 highlights unique features and classification outside of conventional mammalian Gα subfamilies. E. histolytica trophozoites overexpressing wildtype EhGα1 in an inducible manner exhibit an enhanced ability to kill host cells that may be wholly or partially due to enhanced host cell attachment. EhGα1-overexpressing trophozoites also display enhanced transmigration across a Matrigel barrier, an effect that may result from altered baseline migration. Inducible expression of a dominant negative EhGα1 variant engenders the converse phenotypes. Transcriptomic studies reveal that modulation of pathogenesis-related trophozoite behaviors by perturbed heterotrimeric G-protein expression includes transcriptional regulation of virulence factors and altered trafficking of cysteine proteases. Collectively, our studies suggest that E. histolytica possesses a divergent heterotrimeric G-protein signaling axis that modulates key aspects of cellular processes related to the pathogenesis of this infectious organism.

Indexed as

AnimalsCHO CellsCricetinaeCricetulusCrystallography, X-RayEntamoeba histolyticaEntamoebiasisGene Expression RegulationGTP-Binding Protein alpha SubunitsGuanine Nucleotide Exchange FactorsHumansJurkat CellsProtein Structure, TertiaryProtozoan ProteinsRho Guanine Nucleotide Exchange FactorsTranscription, GeneticGTP-Binding Protein alpha SubunitsGuanine Nucleotide Exchange FactorsProtozoan ProteinsRho Guanine Nucleotide Exchange FactorsVirulence Factors

Identifiers

PMID23166501
PMCPMC3499586
OpenAlexW2075463900

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.