ArticlePLoS biology2019
Phosphorylation of the VAR2CSA extracellular region is associated with enhanced adhesive properties to the placental receptor CSA.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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.
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.
Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- The exception that proves the rule: Virulence gene expression at the onset of Plasmodium falciparum blood stage infections.PLoS pathogens · 2023Trial
- FIKK1, a member of the FIKK kinase family, phosphorylates VAR2CSA and regulates adhesion of Plasmodium falciparum-infected erythrocytes to the placental receptor CSA.PLoS pathogens · 2026Article
- Phenotypic screens reveal Plasmodium falciparum genetic factors associated with infection of sickle-trait cells.Blood cells, molecules & diseases · 2025Article
- Article
- Malaria: past, present, and future.Signal transduction and targeted therapy · 2025Review
- Casein Kinases 2-dependent phosphorylation of the placental ligand VAR2CSA regulates Plasmodium falciparum-infected erythrocytes cytoadhesion.PLoS pathogens · 2025Article
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- Sickle Cell Trait Modulates the Proteome and Phosphoproteome ofFrontiers in cellular and infection microbiology · 2021Article
- Poor Birth Outcomes in Malaria in Pregnancy: Recent Insights Into Mechanisms and Prevention Approaches.Frontiers in immunology · 2021Review
- Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for carbohydrate binding.The Journal of biological chemistry · 2020Article
- An exported kinase family mediates species-specific erythrocyte remodelling and virulence in human malaria.Nature microbiology · 2020Article
- Article
- VAR2CSA-Mediated Host Defense Evasion ofFrontiers in immunology · 2020Review
- Placental malaria vaccine candidate antigen VAR2CSA displays atypical domain architecture in someCommunications biology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasmodium falciparum is the main cause of disease and death from malaria. P. falciparum virulence resides in the ability of infected erythrocytes (IEs) to sequester in various tissues through the interaction between members of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesin family to various host receptors. Here, we investigated the effect of phosphorylation of variant surface antigen 2-CSA (VAR2CSA), a member of the PfEMP1 family associated to placental sequestration, on its capacity to adhere to chondroitin sulfate A (CSA) present on the placental syncytium. We showed that phosphatase treatment of IEs impairs cytoadhesion to CSA. MS analysis of recombinant VAR2CSA phosphosites prior to and after phosphatase treatment, as well as of native VAR2CSA expressed on IEs, identified critical phosphoresidues associated with CSA binding. Site-directed mutagenesis on recombinant VAR2CSA of 3 phosphoresidues localised within the CSA-binding region confirmed in vitro their functional importance. Furthermore, using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 nuclease (CRISPR/Cas9), we generated a parasite line in which the phosphoresidue T934 is changed to alanine and showed that this mutation strongly impairs IEs cytoadhesion to CSA. Taken together, these results demonstrate that phosphorylation of the extracellular region of VAR2CSA plays a major role in IEs cytoadhesion to CSA and provide new molecular insights for strategies aiming to reduce the morbidity and mortality of PM.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.