title: Erythrocyte surface glycosylphosphatidyl inositol anchored receptor for the malaria parasite.
abstract: Parasitophorous vacuole formation is a critical step for the successful invasion of host erythrocytes by the malaria parasite. Rhoptry proteins are believed to have essential roles in vacuole formation, although their biological roles are poorly understood. To understand the molecular interactions between parasite rhoptry proteins and the erythrocyte during invasion, we have characterized the binding specificity of the high molecular mass rhoptry protein (RhopH) complex to erythrocytes using the rodent malaria parasite, Plasmodium yoelii. RhopH complex binding to erythrocytes was species-specific, observed with mouse but not rabbit or human erythrocytes. Binding is abolished following treatment of erythrocytes with trypsin or chymotrypsin. Because host cell cholesterol-rich membrane domains are recruited into the nascent parasitophorous vacuole, we evaluated a possible role of RhopH complex binding to the cholesterol-rich membrane domain-associated glycosylphosphatidyl inositol (GPI)-anchored protein. Using chimeric mice harboring GPI-deficient erythrocytes, RhopH complex binding to GPI-deficient mouse erythrocytes was undetectable, indicating involvement of GPI-anchored protein in PyRhopH complex binding. Furthermore, a significant reduction of P. yoelii parasite infection of GPI-deficient erythrocytes was observed in vivo, probably due to inefficient invasion. We conclude that the major erythrocyte receptor for PyRhopH complex is a protein attached to the erythrocyte surface via GPI-anchor and that GPI-deficient erythrocytes are resistant to P. yoelii invasion.
authors.affiliation: Department of Molecular Parasitology, Ehime University School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Thanaporn
authors.initials: T
authors.lastname: Rungruang
authors.forename: Osamu
authors.initials: O
authors.lastname: Kaneko
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Murakami
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamamoto
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Akimitsu
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sekimizu
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Motomi
authors.initials: M
authors.lastname: Torii
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism*; D002918:Chymotrypsin; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D010961:Plasmodium / Q000378:metabolism*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D014357:Trypsin
chemical_list: D000953:Antigens, Protozoan; D017261:Glycosylphosphatidylinositols; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; C065352:rhoptry associated protein, Plasmodium; D002918:Chymotrypsin; D014357:Trypsin