title: Identification of a stomatin orthologue in vacuoles induced in human erythrocytes by malaria parasites. A role for microbial raft proteins in apicomplexan vacuole biogenesis.
abstract: When the human malaria parasite Plasmodium falciparum infects erythrocytes, proteins associated with host-derived detergent-resistant membrane (DRM) rafts are selectively recruited into the newly formed vacuole, but parasite proteins that contribute to raft-based vacuole development are unknown. In mammalian cells, DRM-associated integral membrane proteins such as caveolin-1 and flotillin-1 that form oligomers have been linked to the formation of DRM-based invaginations called caveolae. Here we show that the P. falciparum genome does not encode caveolins or flotillins but does contain an orthologue of human band 7 stomatin, a protein known to oligomerize, associate with non-caveolar DRMs and is distantly related to flotillins. Stomatins are members of a large protein family conserved in evolution and P. falciparum (Pf) stomatin appears to be a prokaryotic-like molecule. Evidence is presented that it associates with DRMs and may oligomerize, suggesting that these features are conserved in the stomatin family. Further, Pfstomatin is an integral membrane protein concentrated at the apical end of extracellular parasites, where it co-localizes with invasion-associated rhoptry organelles. A resident rhoptry protein, RhopH2 also resides in DRMs. This provides the first evidence that rhoptries of an apicomplexan parasite contain DRM rafts. Further, when the parasite invades erythrocytes, rhoptry Pfstomatin and RhopH2 are inserted into the newly formed vacuole. Thus, like caveolin-1 and flotillin-1, a stomatin may also associate with non-clathrin coated, DRM-enriched vacuoles. We propose a new model of invasion and vacuole formation involving DRM-based interactions of both host and parasite molecules.
authors.affiliation: Department of Pathology, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: N Luisa
authors.initials: NL
authors.lastname: Hiller
authors.forename: Thomas
authors.initials: T
authors.lastname: Akompong
authors.forename: Jon S
authors.initials: JS
authors.lastname: Morrow
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Holder
authors.forename: Kasturi
authors.initials: K
authors.lastname: Haldar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry* / Q000235:genetics; D015153:Blotting, Western; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism* / Q000382:microbiology*; D019084:Fluorescent Antibody Technique, Indirect; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000378:metabolism / Q000472:pathogenicity; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013744:Tetanus Toxin / Q000737:chemistry; D013997:Time Factors; D014617:Vacuoles / Q000378:metabolism
chemical_list: D001798:Blood Proteins; C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C036860:STOM protein, human; C406287:STOML2 protein, human; D013744:Tetanus Toxin; C106354:flotillins; D049452:Green Fluorescent Proteins; C026167:tetanolysin