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The ins and outs of nuclear trafficking: unusual aspects in apicomplexan parasites.

ABSTRACT: Apicomplexa is a phylum within the kingdom Protista that contains some of the most significant threats to public health. One of the members of this phylum, Toxoplasma gondii, is amenable to molecular genetic analyses allowing for the identification of factors critical for colonization and disease. A pathway found to be important for T. gondii pathogenesis is the Ran network of nuclear trafficking. Bioinformatics analysis of apicomplexan genomes shows that while Ran is well conserved, the key regulators of Ran--Regulator of Chromosome Condensation 1 and Ran GTPase activating protein--are either highly divergent or absent. Likewise, several import and export receptor molecules that are crucial for nuclear transport are either not present or have experienced genetic drift such that they are no longer recognizable by bioinformatics tools. In this minireview we describe the basics of nuclear trafficking and compare components within apicomplexans to defined systems in humans and yeast. A detailed analysis of the nuclear trafficking network in these eukaryotes is required to understand how this potentially unique cellular biological pathway contributes to host-parasite interactions.

SUBMITTER: Frankel MB

PROVIDER: S-EPMC2903460 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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The ins and outs of nuclear trafficking: unusual aspects in apicomplexan parasites.

Frankel Matthew B MB Knoll Laura J LJ

DNA and cell biology 20090601 6

Apicomplexa is a phylum within the kingdom Protista that contains some of the most significant threats to public health. One of the members of this phylum, Toxoplasma gondii, is amenable to molecular genetic analyses allowing for the identification of factors critical for colonization and disease. A pathway found to be important for T. gondii pathogenesis is the Ran network of nuclear trafficking. Bioinformatics analysis of apicomplexan genomes shows that while Ran is well conserved, the key reg ...[more]

PMID: 19348590

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Project description:Apicomplexans form a large phylum of parasitic protozoa, including the genera Plasmodium, Toxoplasma, and Cryptosporidium, the causative agents of malaria, toxoplasmosis, and cryptosporidiosis, respectively. They cause diseases not only in humans but also in animals, with dramatic consequences in agriculture. Most apicomplexans are vacuole-dwelling and obligate intracellular parasites; as they invade the host cell, they become encased in a parasitophorous vacuole (PV) derived from the host cellular membrane. This creates a parasite-host interface that acts as a protective barrier but also constitutes an obstacle through which the pathogen must import nutrients, eliminate wastes, and eventually break free upon egress. Completion of the parasitic life cycle requires intense remodeling of the infected host cell. Host cell subversion is mediated by a subset of essential effector parasitic proteins and virulence factors actively trafficked across the PV membrane. In the malaria parasite Plasmodium, a unique and highly specialized ATP-driven vacuolar secretion system, the Plasmodium translocon of exported proteins (PTEX), transports effector proteins across the vacuolar membrane. Its core is composed of the three essential proteins EXP2, PTEX150, and HSP101, and is supplemented by the two auxiliary proteins TRX2 and PTEX88. Many but not all secreted malarial effector proteins contain a vacuolar trafficking signal or Plasmodium export element (PEXEL) that requires processing by an endoplasmic reticulum protease, plasmepsin V, for proper export. Because vacuolar parasitic protein export is essential to parasite survival and virulence, this pathway is a promising target for the development of novel antimalarial therapeutics. This review summarizes the current state of structural and mechanistic knowledge on the Plasmodium parasitic vacuolar secretion and effector trafficking pathway, describing its most salient features and discussing the existing differences and commonalities with the vacuolar effector translocation MYR machinery recently described in Toxoplasma and other apicomplexans of significance to medical and veterinary sciences.

Dataset Information

The ins and outs of nuclear trafficking: unusual aspects in apicomplexan parasites.

Publications

The ins and outs of nuclear trafficking: unusual aspects in apicomplexan parasites.

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