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Vacuolar uptake of host components, and a role for cholesterol and sphingomyelin in malarial infection
Author(s) -
Lauer Sabine,
VanWye Jeffrey,
Harrison Travis,
McManus Heather,
Samuel Benjamin U.,
Hiller N.Luisa,
Mohandas Narla,
Haldar Kasturi
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.14.3556
Subject(s) - biology , vacuole , internalization , microbiology and biotechnology , transmembrane protein , intracellular , endocytosis , sphingomyelin , pinocytosis , endocytic cycle , intracellular parasite , cytoplasm , membrane protein , endosome , plasmodium falciparum , biochemistry , cell , membrane , receptor , immunology , malaria
Erythrocytes, which are incapable of endocytosis or phagocytosis, can be infected by the malaria parasite Plasmodium falciparum . We find that a transmembrane protein (Duffy), glycosylphosphatidylinositol (GPI)‐anchored and cytoplasmic proteins, associated with detergent‐resistant membranes (DRMs) that are characteristic of microdomains in host cell membranes, are internalized by vacuolar parasites, while the major integral membrane and cytoskeletal proteins are not. The internalized host proteins and a plasmodial transmembrane resident parasitophorous vacuolar membrane (PVM) protein are detected in DRMs associated with vacuolar parasites. This is the first report of a host transmembrane protein being recruited into an apicomplexan vacuole and of the presence of vacuolar DRMs; it establishes that integral association does not preclude protein internalization into the P.falciparum vacuole. Rather, as shown for Duffy, intracellular accumulation occurs at the same rate as that seen for a DRM‐associated GPI‐anchored protein. Furthermore, novel mechanisms regulated by the DRM lipids, sphingomyelin and cholesterol, mediate (i) the uptake of host DRM proteins and (ii) maintenance of the intracellular vacuole in the non‐endocytic red cell, which may have implications for intracellular parasitism and pathogenesis.