Evidence map›Paper›PMID 31285585›Full record

ArticleNature microbiology2019

CYRI/FAM49B negatively regulates RAC1-driven cytoskeletal remodelling and protects against bacterial infection.

Kyoko E Yuki, Hadir Marei, Evgenij Fiskin, Megan M Eva, Angelica A Gopal, Jeremy A Schwartzentruber, Jacek Majewski, Mathieu Cellier, Judith N Mandl, Silvia M Vidal and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
6.3field-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

32 citing papers in PubMed, 57 citations in OpenAlex.

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  17. Computational prediction and experimental validation ofFrontiers in cellular and infection microbiology · 2022
    Article
  18. Article
  19. Article
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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

12 authors at 4 institutions in 2 countries.

Kyoko E Yuki *Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Hadir Marei *Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.ORCID http://orcid.org/0000-0002-1249-2765
Evgenij Fiskin *Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.
Megan M Eva *Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Angelica A GopalMcGill University Research Centre on Complex Traits, McGill University, Montreal, Quebec, Canada.
Jeremy A SchwartzentruberDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-6183-2092
Jacek MajewskiDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Mathieu CellierInstitut Armand-Frappier, Centre INRS, Laval, Quebec, Canada.
Judith N MandlMcGill University Research Centre on Complex Traits, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0002-6512-3437
Silvia M VidalDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada.
Danielle MaloDepartment of Human Genetics, McGill University, Montreal, Quebec, Canada. danielle.malo@mcgill.ca.ORCID http://orcid.org/0000-0003-3980-6610
Ivan DikicInstitute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany. dikic@biochem2.uni-frankfurt.de.ORCID http://orcid.org/0000-0001-8156-9511
McGill University · CAGoethe University Frankfurt · DEInstitut National de la Recherche Scientifique · CAMcGill Genome Centre · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Salmonella presents a global public health concern. Central to Salmonella pathogenicity is an ability to subvert host defences through strategically targeting host proteins implicated in restricting infection. Therefore, to gain insight into the host-pathogen interactions governing Salmonella infection, we performed an in vivo genome-wide mutagenesis screen to uncover key host defence proteins. This revealed an uncharacterized role of CYRI (FAM49B) in conferring host resistance to Salmonella infection. We show that CYRI binds to the small GTPase RAC1 through a conserved domain present in CYFIP proteins, which are known RAC1 effectors that stimulate actin polymerization. However, unlike CYFIP proteins, CYRI negatively regulates RAC1 signalling, thereby attenuating processes such as macropinocytosis, phagocytosis and cell migration. This enables CYRI to counteract Salmonella at various stages of infection, including bacterial entry into non-phagocytic and phagocytic cells as well as phagocyte-mediated bacterial dissemination. Intriguingly, to dampen its effects, the bacterial effector SopE, a RAC1 activator, selectively targets CYRI following infection. Together, this outlines an intricate host-pathogen signalling interplay that is crucial for determining bacterial fate. Notably, our study also outlines a role for CYRI in restricting infection mediated by Mycobacterium tuberculosis and Listeria monocytogenes. This provides evidence implicating CYRI cellular functions in host defence beyond Salmonella infection.

Indexed as

Signal TransductionActinsAnimalsBacterial InfectionsBacterial LoadBacterial ProteinsCytoskeletonDisease ResistanceHEK293 CellsHeLa CellsHost-Pathogen InteractionsHumansIntracellular Signaling Peptides and ProteinsListeria monocytogenesMacrophagesMiceActinsBacterial ProteinsCYRIB protein, humanIntracellular Signaling Peptides and ProteinsMitochondrial Proteinsrac1 GTP-Binding ProteinSopE protein, Salmonella

Identifiers

PMID31285585
OpenAlexW2962175009

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.