Proteomics approach reveals novel proteins on the surface of malaria-infected erythrocytes

Florens, Laurence; Liu, Xia; Wang, Yufeng; Yang, Shiguang; Schwartz, Owen; Peglar, Michael T.; Carucci, Daniel J.; Yates, John R.; Wu, Yimin

doi:10.1016/j.molbiopara.2003.12.007

Cited by 169 publications

(137 citation statements)

References 28 publications

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“…The most plausible explanation is that the proteins that are expressed on the IRBC surface during the maturation of trophozoites sterically mask the C4S-adhesive protein(s), resulting in decreased IRBC binding capacity. A previous study has shown that a number of proteins are expressed on IRBC surface (17), and presumably many of these are expressed during trophozoite development. This interpretation agrees with the observation that the adhesive protein(s) on the surface of IRBCs is more susceptible to trypsin treatment at the late ring and early trophozoite stages than at the late trophozoite stage.…”

Section: Discussionmentioning

confidence: 99%

Developmental Stage- and Cell Cycle Number-Dependent Changes in Characteristics of Plasmodium falciparum -Infected Erythrocyte Adherence to Placental Chondroitin-4-Sulfate Proteoglycan

2007

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The adherence of Plasmodium falciparum-infected red blood cells (IRBCs) in the human placenta is mediated by chondroitin-4-sulfate (C4S). Although IRBC binding to C4S has been unequivocally established, the adherence characteristics of IRBCs at different stages of parasite development and through successive parasite generations after selection for C4S adherence are not known. Here we show that IRBCs acquire a significant capacity to bind to C4S at as early as 14 h and exhibit maximum binding at 22 to 26 h postinvasion. Surprisingly, the IRBC binding ability decreases by ϳ50% at the late trophozoite and schizont stages. The binding strength of the IRBCs also gradually decreases during successive generations after selection for C4S binding, and at the 32nd generation, the binding capacity was only ϳ31% of that of IRBCs at the 2nd generation, suggesting that IRBCs eventually lose their C4S-adherent capacity. We also tested the susceptibility of the adhesive protein(s) on the IRBC surface to trypsin treatment at different stages of parasite development. The data show that IRBCs with late trophozoites are more resistant to trypsin treatment than those containing early trophozoites, indicating that parasite proteins expressed on the IRBC surface during trophozoite maturation partially mask accessibility of adhesive protein for binding to C4S. These data provide important insights into the expression pattern of the C4S-adhesive protein(s) on the IRBC surface, emphasizing the need for understanding the regulation of genes involved in IRBC binding to C4S. Our data also define the parasite stage at which IRBCs are suitable for studying structural interactions with C4S.

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Section: Discussionmentioning

confidence: 99%

Developmental Stage- and Cell Cycle Number-Dependent Changes in Characteristics of Plasmodium falciparum -Infected Erythrocyte Adherence to Placental Chondroitin-4-Sulfate Proteoglycan

2007

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“…Proteomics was also successfully employed to analyze invasion of malaria parasites into human red blood cells [112]. Two novel surface proteins were identified by Florens et al [113] on Plasmodium falciparuminfected erythrocytes. A restricted number of red blood cell membrane proteins such as flotillin-1, syntaxin 1C, and arginase, appear to be dysregulated in diabetic type 2 patients [114].…”

Section: Red Blood Cellsmentioning

confidence: 99%

Recent advances in blood‐related proteomics

et al. 2005

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Service régional vaudois de transfusion sanguine, Lausanne, SwitzerlandBlood is divided in two compartments, namely, plasma and cells. The latter contain red blood cells, leukocytes, and platelets. From a descriptive medical discipline, hematology has evolved towards a pioneering discipline where molecular biology has permitted the development of prognostic and diagnostic indicators for disease. The recent advance in MS and protein separation now allows similar progress in the analysis of proteins. Proteomics offers great promise for the study of proteins in plasma/serum, indeed a number of proteomics databases for plasma/ serum have been established. This is a very complex body fluid containing lipids, carbohydrates, amino acids, vitamins, nucleic acids, hormones, and proteins. About 1500 different proteins have recently been identified, and a number of potential new markers of diseases have been characterized. Here, examples of the enormous promise of plasma/serum proteomic analysis for diagnostic/prognostic markers and information on disease mechanism are given. Within the blood are also a large number of different blood cell types that potentially hold similar information. Proteomics of red blood cells, until now, has not improved our knowledge of these cells, in contrast to the major progresses achieved while studying platelets and leukocytes. In the future, proteomics will change several aspects of hematology.

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“…A number of studies have identified Plasmodium proteins that contain signature sequence motifs, the host cell targeting signal or the Plasmodium export element (PEXEL), that target these proteins into the infected erythrocytes (10,11). Recent proteomics analyses have identified novel proteins in the raftlike membranes of the parasite and on the surface of infected erythrocytes (12,13). P. falciparum translationally controlled tumor protein (PfTCTP), a homolog of the mammalian histamine-releasing factor, has been shown to be released into the culture supernatant from intact as well as ruptured infected RBCs and causes histamine release from human basophils and IL-8 secretion from eosinophils (14).…”

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confidence: 99%

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

Singh

Mukherjee

Narayanasamy³

et al. 2009

Molecular & Cellular Proteomics

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The highly co-evolved relationship of parasites and their hosts appears to include modulation of host immune signals, although the molecular mechanisms involved in the host-parasite interplay remain poorly understood. Characterization of these key genes and their cognate proteins related to the host-parasite interplay should lead to a better understanding of this intriguing biological phenomenon. The malaria agent Plasmodium falciparum is predicted to export a cohort of several hundred proteins to remodel the host erythrocyte. However, proteins actively exported by the asexual intracellular parasite beyond the host red blood cell membrane (before merozoite egress) have been poorly investigated so far. Here we used two complementary methodologies, two-dimensional gel electrophoresis/MS and LC-MS/MS, to examine the extracellular secreted antigens at asexual blood stages of P. falciparum. We identified 27 novel antigens exported by P. falciparum in the culture medium of which some showed clustering with highly polymorphic genes on chromosomes, suggesting that they may encode putative antigenic determinants of the parasite. Immunolocalization of four novel secreted proteins confirmed their export beyond the infected red blood cell membrane. Of these, preliminary functional characterization of two novel (Sel1 repeat-containing) parasite proteins, PfSEL1 and PfSEL2 revealed that they down-regulate expression of cell surface Notch signaling molecules in host cells. Also a novel protein kinase (PfEK) and a novel protein phosphatase (PfEP) were found to, respectively, phosphorylate/dephosphorylate parasite-specific proteins in the extracellular culture supernatant. Our study thus sheds new light on malaria parasite extracellular secreted antigens of which some may be essential for parasite development and could constitute promising new drug targets. Molecular & Cellular Proteomics 8:2102-2118, 2009.

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Proteomics approach reveals novel proteins on the surface of malaria-infected erythrocytes

Cited by 169 publications

References 28 publications

Developmental Stage- and Cell Cycle Number-Dependent Changes in Characteristics of Plasmodium falciparum -Infected Erythrocyte Adherence to Placental Chondroitin-4-Sulfate Proteoglycan

Developmental Stage- and Cell Cycle Number-Dependent Changes in Characteristics of Plasmodium falciparum -Infected Erythrocyte Adherence to Placental Chondroitin-4-Sulfate Proteoglycan

Recent advances in blood‐related proteomics

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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