title: The Plasmodium rhoptry associated protein complex is important for parasitophorous vacuole membrane structure and intraerythrocytic parasite growth.
abstract: Plasmodium parasites must invade erythrocytes in order to cause the disease malaria. The invasion process involves the coordinated secretion of parasite proteins from apical organelles that include the rhoptries. The rhoptry is comprised of two compartments: the neck and the bulb. Rhoptry neck proteins are involved in host cell adhesion and formation of the tight junction that forms between the invading parasite and erythrocyte, whereas the role of rhoptry bulb proteins remains ill-defined due to the lack of functional studies. In this study, we show that the rhoptry-associated protein (RAP) complex is not required for rhoptry morphology or erythrocyte invasion. Instead, post-invasion when the parasite is bounded by a parasitophorous vacuolar membrane (PVM), the RAP complex facilitates the survival of the parasite in its new intracellular environment. Consequently, conditional knockdown of members of the RAP complex leads to altered PVM structure, delayed intra-erythrocytic growth, and reduced parasitaemias in infected mice. This study provides evidence that rhoptry bulb proteins localising to the parasite-host cell interface are not simply by-products of the invasion process but contribute to the growth of Plasmodium in vivo.
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
authors.forename: Sreejoyee
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, Melbourne, Victoria, Australia.
authors.forename: Kit
authors.initials: K
authors.lastname: Kennedy
authors.affiliation: The Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Sanders
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Matthews
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, Melbourne, Victoria, Australia.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Ralph
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Counihan
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
authors.forename: Tania F
authors.identifier: 0000-0001-5810-8063
authors.initials: TF
authors.lastname: de Koning-Ward
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000469:parasitology*; D054884:Host-Pathogen Interactions; D008288:Malaria / Q000469:parasitology; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000502:physiology*; D015800:Protozoan Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000469:parasitology*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D037521:Virulence Factors; C065352:rhoptry associated protein, Plasmodium
keywords: Plasmodium; RAP; host cell remodelling; parasitophorous vacuole; rhoptry