Portal de Periódicos da CAPES

Membrane Transformation during Malaria Parasite Release from Human Red Blood Cells

2005; Elsevier BV; Volume: 15; Issue: 18 Linguagem: Inglês

10.1016/j.cub.2005.07.067

1879-0445

Svetlana Glushakova, Dan Yin, Tao Li, Joshua Zimmerberg,

Complement system in diseases

Three opposing pathways are proposed for the release of malaria parasites [1Miller L.H. Good M.F. Milon G. Malaria pathogenesis.Science. 1994; 264: 1878-1883Crossref PubMed Scopus (462) Google Scholar] from infected erythrocytes [2Bannister L.H. Looking for the exit: how do malaria parasites escape from red blood cells?.Proc. Natl. Acad. Sci. USA. 2001; 98: 383-384Crossref PubMed Scopus (15) Google Scholar, 3Lew V.L. Packaged merozoite release without immediate host cell lysis.Trends Parasitol. 2001; 17: 401-403Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar]: coordinated rupture of the two membranes surrounding mature parasites [4Dvorak J.A. Miller L.H. Whitehouse W.C. Shiroishi T. Invasion of erythrocytes by malaria merozoites.Science. 1975; 187: 748-750Crossref PubMed Scopus (314) Google Scholar, 5Wickham M.E. Culvenor J.G. Cowman A.F. Selective inhibition of a two-step egress of malaria parasites from the host erythrocyte.J. Biol. Chem. 2003; 278: 37658-37663Crossref PubMed Scopus (133) Google Scholar]; fusion of erythrocyte and parasitophorus vacuolar membranes (PVM) [6Winograd E. Clavijo C.A. Bustamante L.Y. Jaramillo M. Release of merozoites from Plasmodium falciparum-infected erythrocytes could be mediated by a non-explosive event.Parasitol. Res. 1999; 85: 621-624Crossref PubMed Scopus (31) Google Scholar, 7Clavijo C.A. Mora C.A. Winograd E. Identification of novel membrane structures in Plasmodium falciparum-infected erythrocytes.Mem. Inst. Oswaldo Cruz. 1998; 93: 115-120Crossref PubMed Scopus (13) Google Scholar, 8Sherman I.W. Eda S. Winograd E. Erythrocyte aging and malaria.Cell. Mol. Biol. 2004; 50: 159-169PubMed Google Scholar]; and liberation of parasites enclosed within the vacuole from the erythrocyte followed by PVM disintegration [9Salmon B.L. Oksman A. Goldberg D.E. Malaria parasite exit from the host erythrocyte: a two-step process requiring extraerythrocytic proteolysis.Proc. Natl. Acad. Sci. USA. 2001; 98: 271-276Crossref PubMed Scopus (188) Google Scholar]. Rupture by cell swelling should yield erythrocyte ghosts; membrane fusion is inhibited by inner-leaflet amphiphiles of positive intrinsic curvature [10Zimmerberg J. Are the curves in all the right places?.Traffic. 2000; 1: 366-368Crossref PubMed Scopus (23) Google Scholar], which contrariwise promote membrane rupture; and without protease inhibitors [9Salmon B.L. Oksman A. Goldberg D.E. Malaria parasite exit from the host erythrocyte: a two-step process requiring extraerythrocytic proteolysis.Proc. Natl. Acad. Sci. USA. 2001; 98: 271-276Crossref PubMed Scopus (188) Google Scholar], parasites would leave erythrocytes packed within the vacuole. Therefore, we visualized erythrocytes releasing P. falciparum using fluorescent microscopy of differentially labeled membranes. Release did not yield erythrocyte ghosts, positive-curvature amphiphiles did not inhibit release but promoted it, and release of packed merozoites was shown to be an artifact. Instead, two sequential morphological stages preceded a convulsive rupture of membranes and rapid radial discharge of separated merozoites, leaving segregated internal membrane fragments and plasma membrane vesicles or blebs at the sites of parasite egress. These results, together with the modulation of release by osmotic stress, suggest a pathway of parasite release that features a biochemically altered erythrocyte membrane that folds after pressure-driven rupture of membranes.