scholarly journals Analyses of Interactions Between Heparin and the Apical Surface Proteins of Plasmodium falciparum

2013 ◽  
Vol 3 (1) ◽  
Author(s):  
Kyousuke Kobayashi ◽  
Ryo Takano ◽  
Hitoshi Takemae ◽  
Tatsuki Sugi ◽  
Akiko Ishiwa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Proteins ◽  
Apical Surface

scholarly journals Erratum: CORRIGENDUM: Analyses of Interactions Between Heparin and the Apical Surface Proteins of Plasmodium falciparum

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Kyousuke Kobayashi ◽  
Ryo Takano ◽  
Hitoshi Takemae ◽  
Tatsuki Sugi ◽  
Akiko Ishiwa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Proteins ◽  
Apical Surface

scholarly journals Interactions between Merozoite Surface Proteins 1, 6, and 7 of the Malaria Parasite Plasmodium falciparum

2006 ◽  
Vol 281 (42) ◽  
pp. 31517-31527
Author(s):  
Christian W. Kauth ◽  
Ute Woehlbier ◽  
Michaela Kern ◽  
Zeleke Mekonnen ◽  
Rolf Lutz ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Surface Proteins ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

scholarly journals How to induce protective humoral immunity against Plasmodium falciparum circumsporozoite protein

2022 ◽  
Vol 219 (2) ◽  
Author(s):  
Ilka Wahl ◽  
Hedda Wardemann
Keyword(s):  
Plasmodium Falciparum ◽  
Immune Responses ◽  
Vaccine Efficacy ◽  
Circumsporozoite Protein ◽  
Surface Proteins ◽  
Humoral Immune ◽  
Cell Responses ◽  
Humoral Immune Responses ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

The induction of protective humoral immune responses against sporozoite surface proteins of the human parasite Plasmodium falciparum (Pf) is a prime goal in the development of a preerythrocytic malaria vaccine. The most promising antibody target is circumsporozoite protein (CSP). Although PfCSP induces strong humoral immune responses upon vaccination, vaccine efficacy is overall limited and not durable. Here, we review recent efforts to gain a better molecular and cellular understanding of anti-PfCSP B cell responses in humans and discuss ways to overcome limitations in the induction of stable titers of high-affinity antibodies that might help to increase vaccine efficacy and promote long-lived protection.

Population genetics of Plasmodium falciparum within a malaria hyperendemic area

Parasitology ◽  
1991 ◽  
Vol 103 (1) ◽  
pp. 7-16 ◽  
Author(s):  
D. J. Conway ◽  
J. S. McBride
Keyword(s):  
Plasmodium Falciparum ◽  
The Gambia ◽  
Surface Proteins ◽  
Urban Region ◽  
Probable Number ◽  
Hyperendemic Area ◽  
Significant Difference ◽  
Genotype Diversity ◽  
Random Assortment ◽  
Exported Protein

Serotyping with monoclonal antibodies was used to estimate the number and frequencies of allelic variants of two merozoite surface proteins, MSP1 and MSP2, and an exported protein Exp-1, in a sample of 344 clinical isolates of Plasmodium falciparum from an urban region of The Gambia. Represented among the isolates were 36, 8 and 2 alleles of the MSP1, MSP2 and Exp-1 loci respectively. Relative frequencies of these alleles remained stable in the parasite population over the 2 years of the study. A computer program was used to calculate from the frequencies of individual alleles at the three loci, the probable number of different genotypes in samples from the population, assuming random assortment among the loci. No significant difference was found between the expected and the observed genotype diversity. It is concluded that recombination among unlinked loci is a common consequence of sexual reproduction of P. falciparum in The Gambia. Slightly lower genotype diversity was observed in each of two villages, which may be a consequence of smaller population size compared with the urban region.

scholarly journals The periciliary ring in polarized epithelial cells is a hot spot for delivery of the apical protein gp135

2015 ◽  
Vol 211 (2) ◽  
pp. 287-294 ◽  
Author(s):  
Emily H. Stoops ◽  
Michael Hull ◽  
Christina Olesen ◽  
Kavita Mistry ◽  
Jennifer L. Harder ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Primary Cilium ◽  
Protein Delivery ◽  
Hot Spot ◽  
Basolateral Membrane ◽  
Protein A ◽  
Surface Proteins ◽  
Apical Surface ◽  
Directed Movement ◽  
Polarized Epithelial Cells

In polarized epithelial cells, newly synthesized cell surface proteins travel in carrier vesicles from the trans Golgi network to the apical or basolateral plasma membrane. Despite extensive research on polarized trafficking, the sites of protein delivery are not fully characterized. Here we use the SNAP tag system to examine the site of delivery of the apical glycoprotein gp135. We show that a cohort of gp135 is delivered to a ring surrounding the base of the primary cilium, followed by microtubule-dependent radial movement away from the cilium. Delivery to the periciliary ring was specific to newly synthesized and not recycling protein. A subset of this newly delivered protein traverses the basolateral membrane en route to the apical membrane. Crumbs3a, another apical protein, was not delivered to the periciliary region, instead making its initial apical appearance in a pattern that resembled its steady-state distribution. Our results demonstrate a surprising “hot spot” for gp135 protein delivery at the base of the primary cilium and suggest the existence of a novel microtubule-based directed movement of a subset of apical surface proteins.

scholarly journals Expressed var genes are found in Plasmodium falciparum subtelomeric regions.

1997 ◽  
Vol 17 (2) ◽  
pp. 604-611 ◽  
Author(s):  
R Hernandez-Rivas ◽  
D Mattei ◽  
Y Sterkers ◽  
D S Peterson ◽  
T E Wellems ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antigenic Variation ◽  
Protein Product ◽  
Terminal Segment ◽  
Surface Proteins ◽  
Var Genes ◽  
Active Expression ◽  
Transmembrane Sequence ◽  
High Level ◽  
Carboxy Terminal

The antigenic variation and cytoadherence of Plasmodium falciparum-infected erythrocytes are modulated by a family of variant surface proteins encoded by the var multigene family. The var genes occur on multiple chromosomes, often in clusters, and 50 to 150 genes are estimated to be present in the haploid parasite genome. Transcripts from var genes have been previously mapped to internal chromosome positions, but the generality of such assignments and the expression sites and mechanisms that control switches of var gene expression are still in early stages of investigation. Here we describe investigations of closely related var genes that occur in association with repetitive elements near the telomeres of P. falciparum chromosomes. DNA sequence analysis of one of these genes (FCR3-varT11-1) shows the characteristic two-exon structure encoding expected var features, including three variable Duffy binding-like (DBL) domains, a transmembrane sequence, and a carboxy-terminal segment thought to anchor the protein product in knobs at the surface of the parasitized erythrocyte. FCR3-varT11-1 cross-hybridizes with var genes located close to the telomeres of many other P. falciparum chromosomes, including a transcribed gene (FCR3-varT3-1) in chromosome 3 of the P. falciparum FCR3 line. The relatively high level transcription from this gene shows that the polymorphic chromosome ends of P. falciparum, which have been proposed to be transcriptionally silent, can be active expression sites for var genes. The pattern of the FCR3-varT11-1 and FCR3-varT3-1 genes are variable between different P. falciparum lines, presumably due to DNA rearrangements. Thus, recombination events in subtelomeric DNA may have a role in the expression of novel var forms.

scholarly journals CRISPR/Cas9 Genome Editing Reveals That the Intron Is Not Essential for var2csa Gene Activation or Silencing in Plasmodium falciparum

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Jessica M. Bryant ◽  
Clément Regnault ◽  
Christine Scheidig-Benatar ◽  
Sebastian Baumgarten ◽  
Julien Guizetti ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Transcriptional Regulation ◽  
Gene Family ◽  
Genome Editing ◽  
Immune Evasion ◽  
Antigenic Variation ◽  
Surface Proteins ◽  
Functional Study ◽  
Monoallelic Expression ◽  
Immune Evasion Mechanism

ABSTRACT Plasmodium falciparum relies on monoallelic expression of 1 of 60 var virulence genes for antigenic variation and host immune evasion. Each var gene contains a conserved intron which has been implicated in previous studies in both activation and repression of transcription via several epigenetic mechanisms, including interaction with the var promoter, production of long noncoding RNAs (lncRNAs), and localization to repressive perinuclear sites. However, functional studies have relied primarily on artificial expression constructs. Using the recently developed P. falciparum clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, we directly deleted the var2csa P. falciparum 3D7_1200600 (Pf3D7_1200600) endogenous intron, resulting in an intronless var gene in a natural, marker-free chromosomal context. Deletion of the var2csa intron resulted in an upregulation of transcription of the var2csa gene in ring-stage parasites and subsequent expression of the PfEMP1 protein in late-stage parasites. Intron deletion did not affect the normal temporal regulation and subsequent transcriptional silencing of the var gene in trophozoites but did result in increased rates of var gene switching in some mutant clones. Transcriptional repression of the intronless var2csa gene could be achieved via long-term culture or panning with the CD36 receptor, after which reactivation was possible with chondroitin sulfate A (CSA) panning. These data suggest that the var2csa intron is not required for silencing or activation in ring-stage parasites but point to a subtle role in regulation of switching within the var gene family. IMPORTANCE Plasmodium falciparum is the most virulent species of malaria parasite, causing high rates of morbidity and mortality in those infected. Chronic infection depends on an immune evasion mechanism termed antigenic variation, which in turn relies on monoallelic expression of 1 of ~60 var genes. Understanding antigenic variation and the transcriptional regulation of monoallelic expression is important for developing drugs and/or vaccines. The var gene family encodes the antigenic surface proteins that decorate infected erythrocytes. Until recently, studying the underlying genetic elements that regulate monoallelic expression in P. falciparum was difficult, and most studies relied on artificial systems such as episomal reporter genes. Our study was the first to use CRISPR/Cas9 genome editing for the functional study of an important, conserved genetic element of var genes—the intron—in an endogenous, episome-free manner. Our findings shed light on the role of the var gene intron in transcriptional regulation of monoallelic expression. IMPORTANCE Plasmodium falciparum is the most virulent species of malaria parasite, causing high rates of morbidity and mortality in those infected. Chronic infection depends on an immune evasion mechanism termed antigenic variation, which in turn relies on monoallelic expression of 1 of ~60 var genes. Understanding antigenic variation and the transcriptional regulation of monoallelic expression is important for developing drugs and/or vaccines. The var gene family encodes the antigenic surface proteins that decorate infected erythrocytes. Until recently, studying the underlying genetic elements that regulate monoallelic expression in P. falciparum was difficult, and most studies relied on artificial systems such as episomal reporter genes. Our study was the first to use CRISPR/Cas9 genome editing for the functional study of an important, conserved genetic element of var genes—the intron—in an endogenous, episome-free manner. Our findings shed light on the role of the var gene intron in transcriptional regulation of monoallelic expression.

scholarly journals Genetic diversity and differentiation in natural Plasmodium falciparum populations inferred by molecular typing of the merozoite surface proteins 1 and 2

2002 ◽  
Vol 35 (5) ◽  
pp. 527-530 ◽  
Author(s):  
Fabrício J.T. Pereira ◽  
José A. Cordeiro ◽  
Erika H.E. Hoffmann ◽  
Marcelo U. Ferreira
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Natural Selection ◽  
Population Differentiation ◽  
Molecular Typing ◽  
Allele Frequencies ◽  
Surface Proteins ◽  
Transmission Dynamics ◽  
Polymorphic Genes

Genetic diversity and differentiation, inferred by typing the polymorphic genes coding for the merozoite surface proteins 1 (Msp-1) and 2 (Msp-2), were compared for 345 isolates belonging to seven Plasmodium falciparum populations from three continents. Both loci yielded similar estimates of genetic diversity for each population, but rather different patterns of between-population differentiation, suggesting that natural selection on these loci, rather than the transmission dynamics of P. falciparum, determines the variation in allele frequencies among populations.

scholarly journals A new method for the capture of surface proteins in Plasmodium falciparum parasitized erythrocyte

2012 ◽  
Vol 6 (06) ◽  
pp. 536-541 ◽  
Author(s):  
Emanuela Ferru ◽  
Anntonella Pantaleo ◽  
Francesco Turrini
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Surface ◽  
Electrophoretic Analysis ◽  
Cytoskeletal Proteins ◽  
Surface Proteins ◽  
New Method ◽  
Major Drawback ◽  
Rbc Membrane ◽  
Wide Range ◽  
Erythrocyte Surface

Introduction: We propose a new method for the selective labeling, isolation and electrophoretic analysis of the Plasmodium falciparum protein exposed on the erythrocyte cell surface. Historically, membrane surface proteins have been isolated using a surface biotinylation followed by capture of biotin-conjugated protein via an avidin/streptavidin-coated solid support. The major drawback of the standard methods has been the labeling of internal proteins due to fast internalization of biotin. Methodology: To solve this problem, we used a biotin label that does not permeate through the membrane. As a further precaution to avoid the purification of non surface exposed proteins, we directly challenged whole labeled cells with avidin coated beads and then solubilized them using non ionic detergents. Results: A marked enrichment of most of the RBC membrane proteins known to face the external surface of the membrane validated the specificity of the method; furthermore, only small amounts of haemoglobin and cytoskeletal proteins were detected. A wide range of P. falciparum proteins were additionally described to be exposed on the erythrocyte surface. Some of them have been previously observed and used as vaccine candidates while a number of newly described antigens have been presently identified. Those antigens require further characterization and validation with additional methods. Conclusion: Surface proteins preparations were very reproducible and identification of proteins by mass spectrometry has been demonstrated to be feasible and effective.

Involvement of CA++ and Calmodulin in the Intracellular Migration of Influenza's Hemagglutinin to the Apical Surface of MDCK Cells

1982 ◽  
Vol 40 ◽  
pp. 30-33
Author(s):  
E. Rodriguez-Boulan ◽  
K.T. Paskiet ◽  
E. Bard
Keyword(s):  
Plasma Membrane ◽  
Mdck Cells ◽  
Viral Envelope ◽  
Surface Proteins ◽  
Apical Surface ◽  
Main Determinant ◽  
Epithelial Cell Lines ◽  
Dog Kidney ◽  
Vesicular Stomatitis ◽  
Integral Proteins

The polarized distribution of surface components between apical and basolateral domains of the plasma membrane constitutes the basis of epithelial function. We are currently studying the mechanisms employed by epithelial cells to segregate different sets of integral proteins in two opposite regions of the plasma membrane. For this purpose, we are utilizing a model system which involves the infection of polarized epithelial cell lines, such as the dog kidney cell line MDCK, with enveloped RNA viruses. Influenza virus and two paramyxoviruses bud from the apical surface regions of MDCK cells, vesicular stomatitis virus (VSV), a rhabdovirus, is assembled instead from the basolateral surface. A main determinant of polarized budding appears to be the addressing of viral envelope glycoproteins to the surface domain that the virus utilizes for budding. The mechanisms and intracellular pathways involved in this sorting are probably the same as those utilized by the cell for its own surface proteins.

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