Evidence map›Paper›PMID 22906355›Full record

ArticleCellular microbiology2012

The arginine-rich N-terminal domain of ROP18 is necessary for vacuole targeting and virulence of Toxoplasma gondii.

Sarah J Fentress, Tobias Steinfeldt, Jonathan C Howard, L David Sibley

Open access · greenAbstract read
In one paragraph

Article in Cellular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

29 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Divergent kinase regulates membrane ultrastructure of theProceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  8. Article
  9. Article
  10. Rhoptry antigens asClinical and experimental vaccine research · 2019
    Review
  11. Clinical microbiology reviews · 2017
    Review
  12. Article
  13. The Expressed MicroRNA-mRNA Interactions ofFrontiers in microbiology · 2017
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  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

4 authors at 2 institutions in 2 countries.

Sarah J FentressDepartment of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA.
Tobias Steinfeldt
Jonathan C Howard
L David Sibley
University of Cologne · DEWashington University in St. Louis · US

Funding

MOLECULAR BASIS OF TOXOPLASMOSIS IN AIDS PATIENTSR01AI036629 · NIAID · WASHINGTON UNIVERSITY · PI SIBLEY, L. DAVID · 1994 to 2013
$5.3M
TARGETING ESSENTIAL ROP KINASES IN TOXOPLASMAR01AI082423 · NIAID · WASHINGTON UNIVERSITY · PI SIBLEY, L. DAVID · 2009 to 2015
$2.9M
NIAID NIH HHS R01 AI036629NIAID NIH HHS R01 AI082423PHS HHS A1036629PHS HHS A1084243
6 · The paper itself

Abstract

Toxoplasma gondii uses specialized secretory organelles called rhoptries to deliver virulence determinants into the host cell during parasite invasion. One such determinant called rhoptry protein 18 (ROP18) is a polymorphic serine/threonine kinase that phosphorylates host targets to modulate acute virulence. Following secretion into the host cell, ROP18 traffics to the parasitophorous vacuole membrane (PVM) where it is tethered to the cytosolic face of this host-pathogen interface. However, the functional consequences of PVM association are not known. In this report, we show that ROP18 mutants altered in an arginine-rich domain upstream of the kinase domain fail to associate to the PVM following secretion from rhoptries. During infection, host cells upregulate immunity-related GTPases that localize to and destroy the PVM surrounding the parasites. ROP18 disarms this host innate immune pathway by phosphorylating IRGs in a critical GTPase domain and preventing loading on the PVM. Vacuole-targeting mutants of ROP18 failed to phosphorylate Irga6 and were unable to divert IRGs from the PVM, despite retaining intrinsic kinase activity. As a consequence, these mutants were avirulent in a mouse model of acute toxoplasmosis. Thus, the association of ROP18 with the PVM, mediated by its N-terminal arginine-rich domain, is critical to its function as a virulence determinant.

Indexed as

AnimalsDisease Models, AnimalMiceProtein Serine-Threonine KinasesProtozoan ProteinsSequence DeletionToxoplasmaToxoplasmosis, AnimalVacuolesVirulenceVirulence FactorsProtein Serine-Threonine KinasesProtozoan ProteinsROP18 protein, Toxoplasma gondiiVirulence Factors

Identifiers

PMID22906355
PMCPMC3683533
OpenAlexW1571960952

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.