Toxoplasma gondii Targets a Protein Phosphatase 2C to the Nuclei of Infected Host Cells
Luke A. Gilbert,Sandeep Ravindran,Jay M. Turetzky,John C. Boothroyd,Peter J. Bradley,Peter J. Bradley +5 more
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TLDR
The delivery of parasite effector proteins via the rhoptries provides a novel mechanism for Toxoplasma to directly access the command center of its host cell during infection by the parasite.Abstract:
Intracellular pathogens have evolved a wide array of mechanisms to invade and co-opt their host cells for intracellular survival. Apicomplexan parasites such as Toxoplasma gondii employ the action of unique secretory organelles named rhoptries for internalization of the parasite and formation of a specialized niche within the host cell. We demonstrate that Toxoplasma gondii also uses secretion from the rhoptries during invasion to deliver a parasite-derived protein phosphatase 2C (PP2C-hn) into the host cell and direct it to the host nucleus. Delivery to the host nucleus does not require completion of invasion, as evidenced by the fact that parasites blocked in the initial stages of invasion with cytochalasin D are able to target PP2C-hn to the host nucleus. We have disrupted the gene encoding PP2C-hn and shown that PP2C-hn-knockout parasites exhibit a mild growth defect that can be rescued by complementation with the wild-type gene. The delivery of parasite effector proteins via the rhoptries provides a novel mechanism for Toxoplasma to directly access the command center of its host cell during infection by the parasite.read more
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Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue
Jeroen P. J. Saeij,S. Coller,Jon P. Boyle,Maria E. Jerome,Michael W. White,John C. Boothroyd +5 more
TL;DR: This work uses genetic crosses between type II and III lines to show that strain-specific differences in the modulation of host cell transcription are mediated by a putative protein kinase, ROP16, and provides a new mechanism for how an intracellular eukaryotic pathogen can interact with its host.
Journal ArticleDOI
The Phosphoproteomes of Plasmodium falciparum and Toxoplasma gondii Reveal Unusual Adaptations Within and Beyond the Parasites' Boundaries
TL;DR: A phosphoproteome analysis of peptides enriched from schizont stage P. falciparum and T. gondii tachyzoites provides important information on the role of phosphorylation in the host-pathogen interaction and clues to the evolutionary forces operating on proteinosphorylation motifs in both parasites.
Journal ArticleDOI
Kiss and spit: the dual roles of Toxoplasma rhoptries
TL;DR: A model in which an expansion of host range is a major force that drives rhoptry-protein evolution is proposed, in which one of these kinases has a major effect on host-gene expression, including the modulation of key regulators of the immune response.
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Efficient Gene Replacements in Toxoplasma gondii Strains Deficient for Nonhomologous End Joining
TL;DR: It is revealed that a significant KU-dependent NHEJ DNA repair pathway is present in Toxoplasma gondii, making this genetic background an efficient host for gene targeting to speed postgenome functional analysis and genetic dissection of parasite biology.
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Effects of Toxoplasma gondii Infection on the Brain
TL;DR: The strain (genotype) of T. gondii, genetic factors of the host, and probably the route of infection and the stage of infection of the parasite initiating infection all contribute to the establishment of a balance between the host and the parasite and affect the outcome of the infection.
References
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Book
Antibodies: A Laboratory Manual
Ed Harlow,David P. Lane +1 more
TL;DR: A second edition of Antibodies: A Laboratory Manual is being published in September 2013, Revised, extended and updated by Edward Greenfield of the Dana-Farber Cancer Center, the material has been recast with extensive new information and new chapters have been added.
Journal ArticleDOI
The structure and regulation of protein phosphatases
TL;DR: Four major serine/threonine-specific protein phosphatase catalytic subunits are present in the cytoplasm of animal cells and have broad and overlapping specificities in vitro, and account for virtually all measurable activity in tissue extracts toward a variety of phosphoproteins that regulate metabolism, muscle contractility, and other processes.
Journal ArticleDOI
Transport into and out of the Nucleus
TL;DR: This review focuses on recent discoveries in the field, with an emphasis on the carriers and cofactors involved in transport and on possible mechanisms for movement through the nuclear pores.
Journal ArticleDOI
Targeting Malaria Virulence and Remodeling Proteins to the Host Erythrocyte
TL;DR: It is shown that a conserved pentameric sequence plays a central role in protein export into the host cell and the exported proteome in Plasmodium falciparum is predicted, with implications for the development of new antimalarials.
Journal ArticleDOI
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 López-Estraño,Kasturi Haldar +6 more
TL;DR: Functional studies indicated the predictive value of the signal and its role in targeting virulence proteins to the erythrocyte and implicated its recognition by a receptor/transporter, and bioinformatics predicted a secretome of >320 proteins and conservation of the signals across parasite species.