Molecular genetic strategies in <i>Toxoplasma gondii</i>: close in on a successful invader

Soldati, Dominique

doi:10.1016/0014-5793(96)00572-8

Cited by 13 publications

(4 citation statements)

References 33 publications

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“…The relative ease with which it can be cultivated in vitro , coupled with the development of techniques for its genetic and biochemical manipulation, has resulted in the establishment of T. gondii as a powerful model organism for cell biological studies of intracellular parasitism, particularly for the phylum Apicomplexa, which includes several medically and economically important pathogens, e.g. Plasmodium (the causative agent of malaria), Eimeria , Theileria , Cryptosporidium and Babesia ( Soldati, 1996). Moreover, as a primitive eukaryote which contains readily recognizable homologues of mammalian cell compartments and structures, in addition to an assortment of unique specialized organelles, it should provide valuable insight into the evolution of cell processes, e.g.…”

Section: Introductionmentioning

confidence: 99%

Cytoplasmic tail motifs mediate endoplasmic reticulum localization and export of transmembrane reporters in the protozoan parasite Toxoplasma gondii

Hoppe¹,

Joiner²

2000

Cell Microbiol

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In mammalian cells and yeasts, amino acid motifs in the cytoplasmic tails of transmembrane proteins play a prominent role in protein targeting in the early secretory pathway by mediating localization to or rapid export from the endoplasmic reticulum (ER). However, early sorting events are poorly characterized in protozoan parasites. Here, we show that a C‐terminal QKTT sequence mediates the ER localization of chimeric reporter constructs consisting of bacterial alkaline phosphatase (BAP) fused to the transmembrane domain (TMD) and truncated cytoplasmic tail of the human low‐density lipoprotein receptor (LDL) receptor or of murine lysosome‐associated membrane protein (lamp‐1) in Toxoplasma gondii. The cytoplasmic tail of human TGN46 also determines ER localization of BAP chimeras in the parasite, but this can be overcome by the addition at the C‐terminus of the tail of an acidic patch, which functions as an ER export signal in conjunction with an upstream tyrosine motif. These results suggest that COPI‐dependent ER retrieval and COPII‐dependent export mechanisms mediated by KKXX and DXE motifs of mammalian cells are generally conserved in T. gondii. In contrast, the failure of the QKTT motif and TGN46 cytoplasmic tail to induce steady‐state ER localization of vesicular stomatitis virus glycoprotein (VSVG) chimeras in HeLa and NRK cells indicates that significant differences in early secretory trafficking also exist.

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Section: Introductionmentioning

confidence: 99%

Cytoplasmic tail motifs mediate endoplasmic reticulum localization and export of transmembrane reporters in the protozoan parasite Toxoplasma gondii

Hoppe¹,

Joiner²

2000

Cell Microbiol

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“…What is the signal that triggers their release? For T. gondii the development of a DNA transfection system has provided a new tool for exploring molecular aspects of important processes such as invasion and dierentiation (Soldati 1996).…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of cDNA clones encoding a 32-kDa dense-granule antigen of Sarcocystis muris (Apicomplexa)

Freyer¹,

Eschenbacher²,

Mehlhorn

et al. 1998

Parasitology Research

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A monoclonal antibody (2F4) directed against a 32-kDa dense-granule antigen of Sarcocystis muris cyst merozoites (bradyzoites) was used to screen a lambda ZAP cDNA expression library. A clone with an insert of 1.4 kb in length (DG 32/1) was isolated. A fusion protein derived from bacteria harbouring the recombinant plasmid DG 32/1 reacted with monoclonal antibody (mAb) 2F4. Southern blot hybridization suggests that the gene is present as a single copy. On Northern blots, a single mRNA species of 1.8 kb was detected by a cDNA-derived probe. In addition, we isolated a full-length clone (DG 32/PH1) by screening the cDNA library with a non-radioactive-labelled cDNA probe. The nucleotide sequence of DG 32/PH1 comprises 1.57 kb. It contains an open reading frame of 882 bp with a coding capacity of approximately 32 kDa. The hypothetical polypeptide consists of a putative N-terminal signal peptide and the mature protein sequence. The occurrence of an N-terminal signal sequence is consistent with the observation that the 32-kDa protein of S. muris is secreted from the dense granules.

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“…The development of a wide range of molecular genetics tools for T. gondii, such as transformation and a variety of gene disruption technologies, has propelled this organism into the forefront of parasite genetics (Donald and Roos, 1993, 1998Sibley et al, 1993;Soldati, 1996;Boothroyd et al, 1997;Roos et al, 1997;Black and Boothroyd, 1998;Brecht et al, 1999;Soete et al, 1999;Knoll et al, 2001;Sibley et al, 2002). Although some of these techniques have also been developed for parasites such as Plasmodium species (de Koning-Ward et al, 2000;Cowman et al, 2002), and are probably easily transferable to others such as N. caninum (Howe and Sibley, 1997), advanced genetic manipulations are currently impossible for many others such as Eimeria or Sarcocystis.…”

Section: Genetic Manipulation Of Parasitesmentioning

confidence: 99%

Genomics and Its Impact on Parasitology and the Potential for Development of New Parasite Control Methods

Ellis

Morrison²,

Reichel³

2003

DNA and Cell Biology

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Parasitic organisms remain the scourge of the developed and underdeveloped worlds. Malaria, schistosomiasis, leishmaniasis, and trypanosomiasis, for example, still result in a large number of human deaths each year worldwide, while drug resistance among nematodes still poses a major problem to the livestock industries. Genome projects involving parasitic organisms are now abundant, and technologies for the investigations of the parasite transcriptome and proteome are well established. There is no doubt the era of the "omics" is with parasitology, and current trends in the discipline are addressing fundamental biological questions that can make best use of the new technologies, as well as the vast amount of new data being generated. Will this become the "golden age of molecular parasitology," leading to the control of parasitic diseases that have plagued mankind for hundreds of years? The primary aim of this paper is to review advances in the general area of parasite genomics, and to outline where the application of "omics" technologies can and have impacted on the development of new control methods for parasitic organisms.

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Molecular genetic strategies in Toxoplasma gondii: close in on a successful invader

Cited by 13 publications

References 33 publications

Cytoplasmic tail motifs mediate endoplasmic reticulum localization and export of transmembrane reporters in the protozoan parasite Toxoplasma gondii

Cytoplasmic tail motifs mediate endoplasmic reticulum localization and export of transmembrane reporters in the protozoan parasite Toxoplasma gondii

Isolation and characterization of cDNA clones encoding a 32-kDa dense-granule antigen of Sarcocystis muris (Apicomplexa)

Genomics and Its Impact on Parasitology and the Potential for Development of New Parasite Control Methods

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