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Blood, 15 September 2007, Vol. 110, No. 6, pp. 2132-2139. Prepublished online as a Blood First Edition Paper on May 25, 2007; DOI 10.1182/blood-2007-04-083873. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2007-04-083873v1 110/6/2132    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Murphy, S. C. Articles by Haldar, K. Search for Related Content PubMed PubMed Citation Articles by Murphy, S. C. Articles by Haldar, K. Related Collections Red Cells Cytoskeleton Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Cytoplasmic remodeling of erythrocyte raft lipids during infection by the human malaria parasite Plasmodium falciparum Sean C. Murphy1,2, Sebastian Fernandez-Pol1,2, Paul H. Chung1, S. N. Prasanna Murthy1, Stephen B. Milne4, Marcela Salomao5, H. Alex Brown4, Jon W. Lomasney1,3, Narla Mohandas5, and Kasturi Haldar1,2 1 Department of Pathology, 2 Department of Microbiology-Immunology, and 3 Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, IL; 4 Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN; and 5 New York Blood Center, New York, NY Studies of detergent-resistant membrane (DRM) rafts in mature erythrocytes have facilitated identification of proteins that regulate formation of endovacuolar structures such as the parasitophorous vacuolar membrane (PVM) induced by the malaria parasite Plasmodium falciparum. However, analyses of raft lipids have remained elusive because detergents interfere with lipid detection. Here, we use primaquine to perturb the erythrocyte membrane and induce detergent-free buoyant vesicles, which are enriched in cholesterol and major raft proteins flotillin and stomatin and contain low levels of cytoskeleton, all characteristics of raft microdomains. Lipid mass spectrometry revealed that phosphatidylethanolamine and phosphatidylglycerol are depleted in endovesicles while phosphoinositides are highly enriched, suggesting raft-based endovesiculation can be achieved by simple (non–receptor-mediated) mechanical perturbation of the erythrocyte plasma membrane and results in sorting of inner leaflet phospholipids. Live-cell imaging of lipid-specific protein probes showed that phosphatidylinositol (4,5) bisphosphate (PIP2) is highly concentrated in primaquine-induced vesicles, confirming that it is an erythrocyte raft lipid. However, the malarial PVM lacks PIP2, although another raft lipid, phosphatidylserine, is readily detected. Thus, different remodeling/sorting of cytoplasmic raft phospholipids may occur in distinct endovacuoles. Importantly, erythrocyte raft lipids recruited to the invasion junction by mechanical stimulation may be remodeled by the malaria parasite to establish blood-stage infection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Groebel, K. Hoelzle, M. M. Wittenbrink, U. Ziegler, and L. E. Hoelzle Mycoplasma suis Invades Porcine Erythrocytes Infect. Immun., February 1, 2009; 77(2): 576 - 584. [Abstract] [Full Text] [PDF] S. Bhattacharjee, C. van Ooij, B. Balu, J. H. Adams, and K. Haldar Maurer's clefts of Plasmodium falciparum are secretory organelles that concentrate virulence protein reporters for delivery to the host erythrocyte Blood, February 15, 2008; 111(4): 2418 - 2426. [Abstract] [Full Text] [PDF]

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