The high molecular mass rhoptry protein, RhopH1, is encoded by members of the clag multigene family in Plasmodium falciparum and Plasmodium yoelii

Kaneko, O.; Tsuboi, Takafumi; Ling, Irene T.; Howell, Steven; Shirano, Michinori; Tachibana, Masashi; Cao, Yaming; Holder, Anthony A.; Torii, Motomi

doi:10.1016/s0166-6851(01)00391-7

Cited by 82 publications

(66 citation statements)

References 28 publications

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“…rhoph2 and rhoph3, genes whose products make stable interactions with CLAG proteins (31,32), were also examined. In synchronous trophozoite-stage cultures, the wild-type FCB parent expressed clag3.1 at levels that were 42 Ϯ 16-fold higher than the constitutively expressed control gene, PF07_0073 (Fig.…”

Section: Blasticidin S Resistance Is Not Linked To Dna Levelmentioning

confidence: 99%

An Epigenetic Antimalarial Resistance Mechanism Involving Parasite Genes Linked to Nutrient Uptake

Sharma

Wollenberg

Sellers

et al. 2013

Journal of Biological Chemistry

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Background: Malaria parasites acquire antimalarial resistance through incompletely understood mechanisms. Results: Resistance to blasticidin S results from reversible silencing of parasite clag genes through histone modifications without DNA level changes. Conclusion: Sophisticated epigenetic control of clag genes permits regulated control of nutrient and antimalarial transport at the host membrane. Significance: This resistance mechanism allows rapid parasite adaptation to environmental pressures and is worrisome for drug discovery efforts.

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Section: Blasticidin S Resistance Is Not Linked To Dna Levelmentioning

confidence: 99%

An Epigenetic Antimalarial Resistance Mechanism Involving Parasite Genes Linked to Nutrient Uptake

Sharma

Wollenberg

Sellers

et al. 2013

Journal of Biological Chemistry

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“…The RhopH complex comprises three distinct components: RhopH1, RhopH2, and RhopH3 [8][9][10][11][12]. The genes encoding RhopH1 are members of the rhoph1/clag gene family, which was originally defined by the cytoadherence linked asexual gene (clag) on chromosome 9 in P. falciparum (clag9) and consists of at least three members; clag2, 3.1, and 9 [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Diversity and evolution of the rhoph1/clag multigene family of Plasmodium falciparum

Iriko

Kaneko

Otsuki

et al. 2008

Molecular and Biochemical Parasitology

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A complex of high molecular mass proteins (PfRhopH) of the human malaria parasite Plasmodium falciparum induces host protective immunity and therefore is a candidate for vaccine development. Understanding the level of polymorphism and the evolutionary processes is important for advancements in both vaccine design and knowledge of the evolution of cell invasion in this parasite. In the present study, we sequenced the entire open reading frames of seven genes encoding the proteins of the PfRhopH complex (rhoph2, rhoph3, and five rhoph1/clag gene paralogs). We found that four rhoph1/clag genes (clag2, 3.1, 3.2, and 8) were highly polymorphic. Amino acid substitutions and indels are predominantly clustered around amino acid positions 1000-1200 of these four rhoph1/clag genes. An excess of nonsynonymous substitutions over synonymous substitutions was detected for clag8 and 9, indicating positive selection. The McDonald-Kreitman test with a Plasmodium reichenowi orthologous sequence also supports positive selection on clag8. Based on the ratio of interspecific genetic distance to intraspecific distance, the time to the most recent common ancestor of the clag2 and 8 polymorphisms was estimated to be 1.89 and 0.87 million years ago, respectively, assuming divergence of P. falciparum and P. reichenowi 6 million years ago. In addition to a copy number polymorphism, gene conversion events were detected for the rhoph1/clag genes on chromosome 3, which likely play a role in increasing the diversity of each locus. Our results indicate that a high diversity of the PfRhopH1/Clag multigene family is maintained by diversifying selection forces over a considerably long period.

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“…The completion of the Plasmodium falciparum genome has provided the basis for the identification of many proteins in sporozoites (5, 12), but very few of these proteins are characterized for their function in sporozoite infectivity and development in the liver. Proteomic and transcript analyses have identified a number of apical organelle and membraneassociated proteins expressed both in sporozoites and merozoites, with many belonging to molecular families conserved among the diverse species of Plasmodium (3,5,7,19,(22)(23)(24).The circumsporozoite protein (CSP) and to a lesser extent the thrombospondin-related anonymous protein (TRAP, or sporozoite surface protein 2 [SSP2]) have been the focus of most research on the sporozoite stages. CSP and TRAP are major sporozoite proteins that are functionally important for sporozoite development in the mosquito stage and are widely considered as important targets for vaccine development.…”

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confidence: 99%

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Antibodies against MAEBL Ligand Domains M1 and M2 Inhibit Sporozoite Development In Vitro

Preiser¹,

Rénia

Singh

et al. 2004

Infect Immun

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MAEBL is a type 1 membrane protein that is implicated in the merozoite invasion of erythrocytes and sporozoite invasion of mosquito salivary glands. This apical organelle protein is structurally similar to the ebl erythrocyte binding proteins, such as EBA-175, except that the tandem ligand domains of MAEBL are similar to part of the extracellular domain of apical membrane antigen 1 and not the Duffy binding-like domain. Although midgut and salivary gland sporozoites are morphologically similar, salivary gland sporozoites undergo a period of new gene expression after infecting the salivary glands, display distinct phenotypic differences, and are more infectious for the mammalian host. The objectives of this project were to determine the molecular form of MAEBL in the infectious salivary gland sporozoites and whether the ligand has a role in the sporozoite development to exoerythrocytic stages in hepatocytes. We determined that MAEBL is newly expressed in salivary gland sporozoites and in a form distinct from what is present in the midgut sporozoites or present in erythrocytic stages. Both ligand domains (M1 and M2) were expressed as part of a full-length membrane form of MAEBL in the salivary gland sporozoites in contrast to the other stages that retain only the M2 ligand domain as part of the membrane form of the protein. Antisera developed against the cysteine-rich regions of the extracellular portion of MAEBL inhibited sporozoite development to exoerythrocytic forms in vitro. Together these data indicate that MAEBL has a role in this third developmental stage in the life cycle of the malaria parasite. Thus, MAEBL is another target for pre-erythrocytic-stage vaccine development against malaria parasites.Malaria is one of the most serious human diseases, causing several million deaths and clinical illness in hundreds of millions of people every year. Infection is spread from person to person by the bite of a Plasmodium-infected anopheline mosquito. Sporozoites injected by the mosquito must infect and develop in a hepatocyte, which can then initiate the bloodstage infection that causes the severe pathogenesis of malaria. Molecules in the apical organelles and on the surface of malaria sporozoites play a role in sporozoite motility and target this infective stage to the liver. The completion of the Plasmodium falciparum genome has provided the basis for the identification of many proteins in sporozoites (5, 12), but very few of these proteins are characterized for their function in sporozoite infectivity and development in the liver. Proteomic and transcript analyses have identified a number of apical organelle and membraneassociated proteins expressed both in sporozoites and merozoites, with many belonging to molecular families conserved among the diverse species of Plasmodium (3,5,7,19,(22)(23)(24).The circumsporozoite protein (CSP) and to a lesser extent the thrombospondin-related anonymous protein (TRAP, or sporozoite surface protein 2 [SSP2]) have been the focus of most research on the sporozoite stages. CSP ...

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The high molecular mass rhoptry protein, RhopH1, is encoded by members of the clag multigene family in Plasmodium falciparum and Plasmodium yoelii

Cited by 82 publications

References 28 publications

An Epigenetic Antimalarial Resistance Mechanism Involving Parasite Genes Linked to Nutrient Uptake

An Epigenetic Antimalarial Resistance Mechanism Involving Parasite Genes Linked to Nutrient Uptake

Diversity and evolution of the rhoph1/clag multigene family of Plasmodium falciparum

Antibodies against MAEBL Ligand Domains M1 and M2 Inhibit Sporozoite Development In Vitro

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