title: Essential Role of the PfRh5/PfRipr/CyRPA Complex during Plasmodium falciparum Invasion of Erythrocytes.
abstract: Plasmodium falciparum parasites in the merozoite stage invade human erythrocytes and cause malaria. Invasion requires multiple interactions between merozoite ligands and erythrocyte receptors. P. falciparum reticulocyte binding homolog 5 (PfRh5) forms a complex with the PfRh5-interacting protein (PfRipr) and Cysteine-rich protective antigen (CyRPA) and binds erythrocytes via the host receptor basigin. However, the specific role that PfRipr and CyRPA play during invasion is unclear. Using P. falciparum lines conditionally expressing PfRipr and CyRPA, we show that loss of PfRipr or CyRPA function blocks growth due to the inability of merozoites to invade erythrocytes. Super-resolution microscopy revealed that PfRipr, CyRPA, and PfRh5 colocalize at the junction between merozoites and erythrocytes during invasion. PfRipr, CyRPA, and PfRipr/CyRPA/PfRh5-basigin complex is required for triggering the Ca(2+) release and establishing the tight junction. Together, these results establish that the PfRh5/PfRipr/CyRPA complex is essential in the sequential molecular events leading to parasite invasion of human erythrocytes.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Volz
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville 3052, Victoria, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Yap
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sisquella
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia.
authors.forename: Jenn K
authors.initials: JK
authors.lastname: Thompson
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia.
authors.forename: Nicholas T Y
authors.initials: NT
authors.lastname: Lim
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia.
authors.forename: Lachlan W
authors.initials: LW
authors.lastname: Whitehead
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Advanced Light Microscopy Facility, EMBL Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Marko
authors.initials: M
authors.lastname: Lampe
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville 3052, Victoria, Australia.
authors.forename: Wai-Hong
authors.initials: WH
authors.lastname: Tham
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia.
authors.forename: Danny
authors.initials: D
authors.lastname: Wilson
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nebl
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville 3052, Victoria, Australia.
authors.forename: Danushka
authors.initials: D
authors.lastname: Marapana
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Triglia
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia.
authors.forename: Wilson
authors.initials: W
authors.lastname: Wong
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Rogers
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville 3052, Victoria, Australia. Electronic address: cowman@wehi.edu.au.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
mesh_terms: D000953:Antigens, Protozoan / Q000378:metabolism*; D051926:Basigin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism; D004705:Endocytosis; D004912:Erythrocytes / Q000469:parasitology*; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions; D006801:Humans; D008853:Microscopy; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000502:physiology*; D011485:Protein Binding; D055503:Protein Multimerization; D015800:Protozoan Proteins / Q000378:metabolism*
chemical_list: D000953:Antigens, Protozoan; D002352:Carrier Proteins; D002413:Cations, Divalent; C000622047:CyRPA protein, Plasmodium falciparum; D015800:Protozoan Proteins; C531020:RH5 protein, Plasmodium falciparum; C000622046:Ripr protein, Plasmodium falciparum; D051926:Basigin; D002118:Calcium