Evidence map›Paper›PMID 26637786›Full record

ArticleBlood2016

A spiral scaffold underlies cytoadherent knobs in Plasmodium falciparum-infected erythrocytes.

Jean M Watermeyer, Victoria L Hale, Fiona Hackett, Daniel K Clare, Erin E Cutts, Ioannis Vakonakis, Roland A Fleck, Michael J Blackman, Helen R Saibil

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

30 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Article
  3. Contact Dynamics of CytoadheringACS infectious diseases · 2025
    Article
  4. Article
  5. Review
  6. Article
  7. Knobs, Adhesion, and Severe Falciparum Malaria.Tropical medicine and infectious disease · 2023
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Host Cytoskeleton Remodeling throughout the Blood Stages of Plasmodium falciparum.Microbiology and molecular biology reviews : MMBR · 2019
    Review
  20. Interplay between Attenuation- and Virulence-Factors ofPathogens (Basel, Switzerland) · 2019
    Review
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

9 authors at 5 institutions in 1 country.

Jean M WatermeyerDepartment of Biological Sciences, Birkbeck, University of London, London, United Kingdom;
Victoria L HaleDepartment of Biological Sciences, Birkbeck, University of London, London, United Kingdom;
Fiona HackettThe Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom;
Daniel K ClareDepartment of Biological Sciences, Birkbeck, University of London, London, United Kingdom;
Erin E CuttsDepartment of Biochemistry, University of Oxford, Oxford, United Kingdom;
Ioannis VakonakisDepartment of Biochemistry, University of Oxford, Oxford, United Kingdom;
Roland A FleckCentre for Ultrastructural Imaging, Kings College, London, United Kingdom; and.
Michael J BlackmanThe Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Helen R SaibilDepartment of Biological Sciences, Birkbeck, University of London, London, United Kingdom;
Birkbeck, University of London · GBUniversity of Oxford · GBKing's College London · GBLondon School of Hygiene & Tropical Medicine · GBThe Francis Crick Institute · GB

Funding

Biotechnology and Biological Sciences Research Council BB/F016948/1Biotechnology and Biological Sciences Research Council BB/L014211Biotechnology and Biological Sciences Research Council BB/L014211/1Medical Research Council G1100013Medical Research Council MC_U117532063Medical Research Council MR/N009274/1Wellcome Trust 088497/Z/09/Z
6 · The paper itself

Abstract

Much of the virulence of Plasmodium falciparum malaria is caused by cytoadherence of infected erythrocytes, which promotes parasite survival by preventing clearance in the spleen. Adherence is mediated by membrane protrusions known as knobs, whose formation depends on the parasite-derived, knob-associated histidine-rich protein (KAHRP). Knobs are required for cytoadherence under flow conditions, and they contain both KAHRP and the parasite-derived erythrocyte membrane protein PfEMP1. Using electron tomography, we have examined the 3-dimensional structure of knobs in detergent-insoluble skeletons of P falciparum 3D7 schizonts. We describe a highly organized knob skeleton composed of a spiral structure coated by an electron-dense layer underlying the knob membrane. This knob skeleton is connected by multiple links to the erythrocyte cytoskeleton. We used immuno-electron microscopy (EM) to locate KAHRP in these structures. The arrangement of membrane proteins in the knobs, visualized by high-resolution freeze-fracture scanning EM, is distinct from that in the surrounding erythrocyte membrane, with a structure at the apex that likely represents the adhesion site. Thus, erythrocyte knobs in P falciparum infection contain a highly organized skeleton structure underlying a specialized region of membrane. We propose that the spiral and dense coat organize the cytoadherence structures in the knob, and anchor them into the erythrocyte cytoskeleton. The high density of knobs and their extensive mechanical linkage suggest an explanation for the rigidification of the cytoskeleton in infected cells, and for the transmission to the cytoskeleton of shear forces experienced by adhering cells.

Indexed as

CytoskeletonErythrocyte MembraneErythrocytesHumansMalaria, FalciparumMembrane ProteinsPlasmodium falciparumMembrane Proteins

Identifiers

PMID26637786
PMCPMC4797390
OpenAlexW2231638149

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.