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The Plasmodium falciparum rhoptry bulb protein RAMA plays an essential role in rhoptry neck morphogenesis and host red blood cell invasion
- Source :
- PLoS Pathogens, PLoS Pathogens, Vol 15, Iss 9, p e1008049 (2019)
- Publication Year :
- 2019
-
Abstract
- The malaria parasite Plasmodium falciparum invades, replicates within and destroys red blood cells in an asexual blood stage life cycle that is responsible for clinical disease and crucial for parasite propagation. Invasive malaria merozoites possess a characteristic apical complex of secretory organelles that are discharged in a tightly controlled and highly regulated order during merozoite egress and host cell invasion. The most prominent of these organelles, the rhoptries, are twinned, club-shaped structures with a body or bulb region that tapers to a narrow neck as it meets the apical prominence of the merozoite. Different protein populations localise to the rhoptry bulb and neck, but the function of many of these proteins and how they are spatially segregated within the rhoptries is unknown. Using conditional disruption of the gene encoding the only known glycolipid-anchored malarial rhoptry bulb protein, rhoptry-associated membrane antigen (RAMA), we demonstrate that RAMA is indispensable for blood stage parasite survival. Contrary to previous suggestions, RAMA is not required for trafficking of all rhoptry bulb proteins. Instead, RAMA-null parasites display selective mislocalisation of a subset of rhoptry bulb and neck proteins (RONs) and produce dysmorphic rhoptries that lack a distinct neck region. The mutant parasites undergo normal intracellular development and egress but display a fatal defect in invasion and do not induce echinocytosis in target red blood cells. Our results indicate that distinct pathways regulate biogenesis of the two main rhoptry sub-compartments in the malaria parasite.<br />Author summary Despite improved control measures over recent decades, malaria is still a considerable health burden across much of the globe. The disease is caused by a single-celled parasite that invades and replicates within host cells. During invasion, the parasite discharges a set of flask-shaped secretory organelles called rhoptries, the contents of which are crucial for invasion as well as for modifications to the host cell that are important for parasite survival. Rhoptry discharge occurs through fusion of the relatively elongated rhoptry neck to the apical surface of the parasite. Different proteins reside within the bulbous rhoptry body and the neck regions, but how these proteins are selectively sent to their correct sub-compartments within the rhoptries and how the rhoptries are formed, is poorly understood. Here we show that a malaria parasite rhoptry bulb protein called rhoptry-associated membrane antigen (RAMA) plays an essential role in rhoptry neck formation and correct trafficking of certain rhoptry neck and bulb proteins. Parasites deficient in RAMA produce malformed rhoptries and–probably as a result—cannot invade host red blood cells. Our work sheds new light on how rhoptries are formed and reveals insights into the mechanism by which the correct sorting of proteins to distinct regions of the rhoptry is regulated.
- Subjects :
- Plasmodium
Erythrocytes
Protozoan Proteins
Artificial Gene Amplification and Extension
Polymerase Chain Reaction
Database and Informatics Methods
Biology (General)
Malaria, Falciparum
Protozoans
0303 health sciences
030302 biochemistry & molecular biology
Malarial Parasites
Eukaryota
3. Good health
Transport protein
Cell biology
Protein Transport
medicine.anatomical_structure
Rhoptry neck
Sequence Analysis
Research Article
QH301-705.5
Bioinformatics
Immunology
Plasmodium falciparum
Antigens, Protozoan
Biology
Research and Analysis Methods
Microbiology
Parasite Replication
Host-Parasite Interactions
03 medical and health sciences
Sequence Motif Analysis
Virology
Organelle
Parasite Groups
Genetics
medicine
Humans
Molecular Biology Techniques
Molecular Biology
030304 developmental biology
Organelles
Rhoptry
Merozoites
Host Cells
Organisms
Membrane Proteins
Biology and Life Sciences
RC581-607
biology.organism_classification
Parasitic Protozoans
Malaria
Red blood cell
Parasitology
Immunologic diseases. Allergy
Apical complex
Apicomplexa
Viral Transmission and Infection
Cloning
Subjects
Details
- ISSN :
- 15537374 and 15537366
- Volume :
- 15
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS pathogens
- Accession number :
- edsair.doi.dedup.....b9af9fa802e236219194f1cb16584c05