Evidence map›Paper›PMID 30315162›Full record

ArticleNature communications2018

Epistasis studies reveal redundancy among calcium-dependent protein kinases in motility and invasion of malaria parasites.

Hanwei Fang, Ana Rita Gomes, Natacha Klages, Paco Pino, Bohumil Maco, Eloise M Walker, Zenon A Zenonos, Fiona Angrisano, Jake Baum, Christian Doerig and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
8.3field-weighted citation impact, top 2% 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

42 citing papers in PubMed, 82 citations in OpenAlex.

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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

13 authors at 7 institutions in 6 countries.

Hanwei FangDepartment of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, CH-1211, Switzerland.
Ana Rita GomesMalaria Programme, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.ORCID http://orcid.org/0000-0001-7684-8815
Natacha KlagesDepartment of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, CH-1211, Switzerland.
Paco PinoDepartment of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, CH-1211, Switzerland.
Bohumil MacoDepartment of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, CH-1211, Switzerland.
Eloise M WalkerFaculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
Zenon A ZenonosMalaria Programme, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK.
Fiona AngrisanoDepartment of Life Sciences, Imperial College London, London, SW7 2AZ, UK.ORCID http://orcid.org/0000-0002-0457-5982
Jake BaumDepartment of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
Christian DoerigDepartment of Microbiology, Infection & Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
David A BakerFaculty of Infectious and Tropical Diseases, London School of Hygiene &Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.ORCID http://orcid.org/0000-0002-5490-8933
Oliver BillkerThe Laboratory for Molecular Infection Medicine Sweden (MIMS), Department of Molecular Biology, Umeå University, Umeå, SE-901 87, Sweden.ORCID http://orcid.org/0000-0003-1716-168X
Mathieu BrochetDepartment of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, CH-1211, Switzerland. Mathieu.Brochet@unige.ch.ORCID http://orcid.org/0000-0003-3911-5537
University of Geneva · CHImperial College London · GBUniversity of London · GBAustralian Regenerative Medicine Institute · AUUmeå University · SEUniversité de Montpellier · FRWellcome Sanger Institute · GB

Funding

EC | European Research Council (ERC) 695596Medical Research Council G1000779Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) BSSGI0_155852Wellcome Trust 098051Wellcome Trust 100993/Z/13/ZWellcome Trust 106240/Z/14/Z
6 · The paper itself

Abstract

In malaria parasites, evolution of parasitism has been linked to functional optimisation. Despite this optimisation, most members of a calcium-dependent protein kinase (CDPK) family show genetic redundancy during erythrocytic proliferation. To identify relationships between phospho-signalling pathways, we here screen 294 genetic interactions among protein kinases in Plasmodium berghei. This reveals a synthetic negative interaction between a hypomorphic allele of the protein kinase G (PKG) and CDPK4 to control erythrocyte invasion which is conserved in P. falciparum. CDPK4 becomes critical when PKG-dependent calcium signals are attenuated to phosphorylate proteins important for the stability of the inner membrane complex, which serves as an anchor for the acto-myosin motor required for motility and invasion. Finally, we show that multiple kinases functionally complement CDPK4 during erythrocytic proliferation and transmission to the mosquito. This study reveals how CDPKs are wired within a stage-transcending signalling network to control motility and host cell invasion in malaria parasites.

Indexed as

AnimalsCalciumCalcium-Calmodulin-Dependent Protein KinasesCyclic GMP-Dependent Protein KinasesEpistasis, GeneticFemaleMalaria, FalciparumMaleMicePlasmodium bergheiPlasmodium falciparumProtein KinasesProtozoan ProteinsCalciumCalcium-Calmodulin-Dependent Protein KinasesCyclic GMP-Dependent Protein KinasesProtein KinasesProtozoan Proteins

Identifiers

PMID30315162
PMCPMC6185908
OpenAlexW2897197595

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.