ArticlePloS one2014
Proteolysis at a specific extracellular residue implicates integral membrane CLAG3 in malaria parasite nutrient channels.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
What it found
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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.
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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.
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Who cites it
35 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- An overview of the interconnectedness of the PEXEL and non-PEXEL mediated protein export iniScience · 2025Review
- Nutrient stress dramatically increases malaria parasite clag2 copy number to increase host cell permeability and enable pathogen survival.PLoS pathogens · 2025Article
- Utilisation of an in vivo malaria model to provide functional proof for RhopH1/CLAG essentiality and conserved orthology with P. falciparum.Journal of biomedical science · 2025Article
- Guanidinium Chloride-Induced Haemolysis Assay to Measure New Permeation Pathway Functionality in Rodent MalariaBiomolecules · 2024Article
- Article
- Novel Ion Channel Genes in Malaria Parasites.Genes · 2024Review
- Article
- Unique Properties of Nutrient Channels onPathogens (Basel, Switzerland) · 2023Review
- The Medicines for Malaria Venture Malaria Box contains inhibitors of protein secretion in Plasmodium falciparum blood stage parasites.Traffic (Copenhagen, Denmark) · 2022Article
- Epigenetics of malaria parasite nutrient uptake, but why?Trends in parasitology · 2022Review
- Article
- RhopH2 and RhopH3 export enables assembly of the RhopH complex on P. falciparum-infected erythrocyte membranes.Communications biology · 2022Article
- Transporter-Mediated Solutes Uptake as Drug Target inFrontiers in pharmacology · 2022Review
- Transport mechanisms at the malaria parasite-host cell interface.PLoS pathogens · 2021Review
- Article
- How Malaria Parasites Acquire Nutrients From Their Host.Frontiers in cell and developmental biology · 2021Review
- Article
- Complex nutrient channel phenotypes despite Mendelian inheritance in a Plasmodium falciparum genetic cross.PLoS pathogens · 2020Article
- Identification of Antimalarial Compounds That Require CLAG3 for Their Uptake byAntimicrobial agents and chemotherapy · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The plasmodial surface anion channel mediates uptake of nutrients and other solutes into erythrocytes infected with malaria parasites. The clag3 genes of P. falciparum determine this channel's activity in human malaria, but how the encoded proteins contribute to transport is unknown. Here, we used proteases to examine the channel's composition and function. While proteases with distinct specificities all cleaved within an extracellular domain of CLAG3, they produced differing degrees of transport inhibition. Chymotrypsin-induced inhibition depended on parasite genotype, with channels induced by the HB3 parasite affected to a greater extent than those of the Dd2 clone. Inheritance of functional proteolysis in the HB3×Dd2 genetic cross, DNA transfection, and gene silencing experiments all pointed to the clag3 genes, providing independent evidence for a role of these genes. Protease protection assays with a Dd2-specific inhibitor and site-directed mutagenesis revealed that a variant L1115F residue on a CLAG3 extracellular loop contributes to inhibitor binding and accounts for differences in functional proteolysis. These findings indicate that surface-exposed CLAG3 is the relevant pool of this protein for channel function. They also suggest structural models for how exposed CLAG3 domains contribute to pore formation and parasite nutrient uptake.
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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.