ArticleScientific reports2015
The Plasmodium palmitoyl-S-acyl-transferase DHHC2 is essential for ookinete morphogenesis and malaria transmission.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- Genome-wide analysis of strand-specific transcription and DNA methylation inFrontiers in microbiology · 2026Article
- Key Regulators of Parasite Biology Viewed Through a Post-Translational Modification Repertoire.Proteomics · 2025Review
- Loss of serine/threonine protein phosphatase 6 severely impairs sexual stage development in malaria parasite Plasmodium berghei.PLoS pathogens · 2025Article
- Global profiling of protein S-palmitoylation in the second-generation merozoites of Eimeria tenella.Parasitology research · 2024Article
- Coordinated regulation of gene expression ineLife · 2024Article
- Review
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- Plasmodium sporozoite disintegration during skin passage limits malaria parasite transmission.EMBO reports · 2022Article
- Article
- Beyond phosphorylation: Putative roles of post-translational modifications in Plasmodium sexual stages.Molecular and biochemical parasitology · 2021Article
- Gliding motility protein LIMP promotes optimal mosquito midgut traversal and infection by Plasmodium berghei.Molecular and biochemical parasitology · 2021Article
- A protein palmitoylation cascade regulates microtubule cytoskeleton integrity in Plasmodium.The EMBO journal · 2020Article
- The Dynamic Roles of the Inner Membrane Complex in the Multiple Stages of the Malaria Parasite.Frontiers in cellular and infection microbiology · 2020Review
- Screening the Pathogen Box for Molecules Active against Plasmodium Sexual Stages Using a New Nanoluciferase-Based Transgenic Line of P. berghei Identifies Transmission-Blocking Compounds.Antimicrobial agents and chemotherapy · 2018Article
- Protein Lipidation in Cell Signaling and Diseases: Function, Regulation, and Therapeutic Opportunities.Cell chemical biology · 2018Review
- Identification and Characterization of a Novel Palmitoyl Acyltransferase as a Druggable Rheostat of Dynamic Palmitoylome inFrontiers in cellular and infection microbiology · 2018Article
- Palmitoylation of Plasmodium alveolins promotes cytoskeletal function.Molecular and biochemical parasitology · 2017Article
- Dynamic protein S-palmitoylation mediates parasite life cycle progression and diverse mechanisms of virulence.Critical reviews in biochemistry and molecular biology · 2017Review
- Protein S-palmitoylation in cellular differentiation.Biochemical Society transactions · 2017Review
- A Malaria Transmission-Blocking (+)-Usnic Acid Derivative Prevents Plasmodium Zygote-to-Ookinete Maturation in the Mosquito Midgut.ACS chemical biology · 2016Article
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The post-translational addition of C-16 long chain fatty acids to protein cysteine residues is catalysed by palmitoyl-S-acyl-transferases (PAT) and affects the affinity of a modified protein for membranes and therefore its subcellular localisation. In apicomplexan parasites this reversible protein modification regulates numerous biological processes and specifically affects cell motility, and invasion of host cells by Plasmodium falciparum merozoites and Toxoplasma gondii tachyzoites. Using inhibitor studies we show here that palmitoylation is key to transformation of zygotes into ookinetes during initial mosquito infection with P. berghei. We identify DHHC2 as a unique PAT mediating ookinete formation and morphogenesis. Essential for life cycle progression in asexual blood stage parasites and thus refractory to gene deletion analyses, we used promoter swap (ps) methodology to maintain dhhc2 expression in asexual blood stages but down regulate expression in sexual stage parasites and during post-fertilization development of the zygote. The ps mutant showed normal gamete formation, fertilisation and DNA replication to tetraploid cells, but was characterised by a complete block in post-fertilisation development and ookinete formation. Our report highlights the crucial nature of the DHHC2 palmitoyl-S-acyltransferase for transmission of the malaria parasite to the mosquito vector through its essential role for ookinete morphogenesis.
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