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A Host-Targeting Signal in Virulence Proteins Reveals a Secretome in Malarial Infection
N. Luisa Hiller,Souvik Bhattacharjee,Christiaan van Ooij,Konstantinos Liolios,Travis Harrison,Carlos Lopez-Estraño,*Kasturi Haldar
Malaria parasites secrete proteins across the vacuolar membraneinto the erythrocyte, inducing modifications linked to diseaseand parasite survival. We identified an 11amino acidsignal required for the secretion of proteins from the Plasmodiumfalciparum vacuole to the human erythrocyte. Bioinformaticspredicted a secretome of >320 proteins and conservation ofthe signal across parasite species. Functional studies indicatedthe predictive value of the signal and its role in targetingvirulence proteins to the erythrocyte and implicated its recognitionby a receptor/transporter. Erythrocyte modification by the parasitemay involve plasmodial heat shock proteins and be vastly morecomplex than hitherto realized.
Departments of Pathology and Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA.
* Present address: Department of Microbiology and Molecular CellSciences, University of Memphis, 3774 Walker Avenue, 409B LifeSciences Building, Memphis, TN 38152, USA.
To whom correspondence should be addressed. E-mail: k-haldar{at}northwestern.edu
Proteome Analysis of Plasmodium falciparum Extracellular Secretory Antigens at Asexual Blood Stages Reveals a Cohort of Proteins with Possible Roles in Immune Modulation and Signaling.
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Mol. Cell. Proteomics
8, 2102-2118
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The Longin Domain Regulates the Steady-State Dynamics of Sec22 in Plasmodium falciparum.
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Eukaryot. Cell
8, 1330-1340
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World Malaria Day 2009: What Malaria Knows about the Immune System That Immunologists Still Do Not.
Towards understanding the virulence functions of RXLR effectors of the oomycete plant pathogen Phytophthora infestans.
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Microbiology
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PLANT CELL
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PLANT CELL
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PLANT CELL
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Eukaryot. Cell
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Eukaryot. Cell
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Adaptive Evolution Has Targeted the C-Terminal Domain of the RXLR Effectors of Plant Pathogenic Oomycetes.
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PLANT CELL
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Bioinformatics
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A Single Binding Site Mediates Resistance- and Disease-Associated Activities of the Effector Protein NIP1 from the Barley Pathogen Rhynchosporium secalis.
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Skeleton-binding protein 1 functions at the parasitophorous vacuole membrane to traffic PfEMP1 to the Plasmodium falciparum-infected erythrocyte surface.
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Eukaryot. Cell
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A Conserved Region in the EBL Proteins Is Implicated in Microneme Targeting of the Malaria Parasite Plasmodium falciparum.
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Phytophthora genome sequences uncover evolutionary origins and mechanisms of pathogenesis..
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Mol. Cell. Proteomics
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A Maurer's cleft-associated protein is essential for expression of the major malaria virulence antigen on the surface of infected red blood cells.
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PLANT CELL
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171, 587-592
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A Malaria Parasite-encoded Vacuolar H+-ATPase Is Targeted to the Host Erythrocyte.
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280, 36841-36847
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Structural and Functional Studies of Interaction between Plasmodium falciparum Knob-associated Histidine-rich Protein (KAHRP) and Erythrocyte Spectrin.
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280, 31166-31171
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Differential Recognition of Highly Divergent Downy Mildew Avirulence Gene Alleles by RPP1 Resistance Genes from Two Arabidopsis Lines.
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PLANT CELL
17, 1839-1850
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Trafficking of the major virulence factor to the surface of transfected P falciparum-infected erythrocytes.
E. Knuepfer, M. Rug, N. Klonis, L. Tilley, and A. F. Cowman (2005)
Blood
105, 4078-4087
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Proteomic Analysis Identifies Novel Proteins of the Maurer's Clefts, a Secretory Compartment Delivering Plasmodium falciparum Proteins to the Surface of Its Host Cell.
L. Vincensini, S. Richert, T. Blisnick, A. Van Dorsselaer, E. Leize-Wagner, T. Rabilloud, and C. Braun Breton (2005)
Mol. Cell. Proteomics
4, 582-593
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