title: A host cell membrane microdomain is a critical factor for organelle discharge by Toxoplasma gondii.
abstract: Host cell microdomains are involved in the attachment, entry, and replication of intracellular microbial pathogens. Entry into the host cell of Toxoplasma gondii and the subsequent survival of this protozoan parasite are tightly coupled with the proteins secreted from organelle called rhoptry. The rhoptry proteins are rapidly discharged into clusters of vesicles, called evacuoles, which are then delivered to parasitophorous vacuoles (PVs) or nucleus. In this study, we examined the roles of two host cell microdomain components, cholesterol and glycosylphosphatidylinositol (GPI), in evacuole formation. The acute depletion of cholesterol from the host cell plasma membrane blocked evacuole formation but not invasion. Whereas the lack of host cell GPI also altered evacuole formation but not invasion, instead inducing excess evacuole formation. The latter effect was not influenced by the evacuole-inhibiting effects of host cell cholesterol depletion, indicating the independent roles of host GPI and cholesterol in evacuole formation. In addition, the excess formation of evacuoles resulted in the enhanced recruitment of host mitochondria and endoplasmic reticulum to PVs, which in turn stimulated the growth of the parasite.
authors.affiliation: Department of Parasitology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennodai, Tsukuba, Ibaraki, Japan.
authors.forename: Michiru
authors.initials: M
authors.lastname: Tahara
authors.affiliation: Department of Parasitology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan; Department of Biochemistry, School of Medicine, Keio University, Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Syed Bilal Ahmad
authors.initials: SB
authors.lastname: Andrabi
authors.affiliation: Department of Parasitology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennodai, Tsukuba, Ibaraki, Japan.
authors.forename: Ryuma
authors.initials: R
authors.lastname: Matsubara
authors.affiliation: Department of Parasitology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan; Department of Tropical Medicine, The Jikei University School of Medicine, Nishi-shinbashi, Minato-ku, Tokyo, Japan.
authors.forename: Hiroka
authors.initials: H
authors.lastname: Aonuma
authors.affiliation: Department of Parasitology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan; Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai, Tsukuba, Ibaraki, Japan. Electronic address: nagamune@niid.go.jp.
authors.forename: Kisaburo
authors.initials: K
authors.lastname: Nagamune
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006790:Host-Parasite Interactions; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism*; D014122:Toxoplasma / Q000254:growth & development* / Q000378:metabolism; D014123:Toxoplasmosis / Q000473:pathology*; D014617:Vacuoles / Q000378:metabolism
chemical_list: D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D015800:Protozoan Proteins; D002784:Cholesterol
keywords: Cholesterol; Evacuole; Glycosylphosphatidylinositol-anchor; Rhoptry protein; Toxoplasma gondii