ApiLoc - A database of published protein sub-cellular localisation in Apicomplexa

version 3 (curated until May 28, 2011)

Discovery of parasite virulence genes reveals a unique regulator of chromosome condensation 1 ortholog critical for efficient nuclear trafficking.

Frankel, M. B., Mordue, D. G., Knoll, L. J. (2007 Jun 12, Proc Natl Acad Sci U S A)

Eukaryotic parasites are a leading cause of morbidity and mortality worldwide, yet little is known about the genetic basis of their virulence. Here, we present a forward genetic screen to study pathogenesis in the protozoan parasite Toxoplasma gondii. By using modified signature-tagged mutagenesis, the growth of 6,300 T. gondii insertional mutants was compared in cell culture and murine infection to identify genes required specifically in vivo. One of the 39 avirulent mutants is disrupted in a divergent ortholog of the regulator of chromosome condensation 1 (RCC1), which is critical for nuclear trafficking in model systems. Although this RCC1 mutant grows similar to wild type in standard tissue culture conditions, it is growth-impaired under nutrient limitation. Genetic complementation of mutant parasites with the T. gondii RCC1 gene fully restores both virulence in mice and growth under low-nutrient conditions. Further analysis shows that there is a significant defect in nuclear trafficking in the RCC1 mutant. These findings suggest that the rate of nuclear transport is a critical factor affecting growth in low-nutrient conditions in vivo and in vitro. Additionally, we observed that although RCC1 proteins are highly conserved in organisms from humans to yeast, no protozoan parasite encodes a characteristic RCC1. This protein divergence may represent a unique mechanism of nucleocytoplasmic transport. This study illustrates the power of this forward genetics approach to identify atypical virulence mechanisms.

PubMed: 17535896, full text

Localisation information

TGME49_013900 (RCC1) regulator of chromosome condensation, putative

Experimental localisation: nucleus during tachyzoite
  • Species: Toxoplasma gondii
  • Quote inferring localisation: "TgRCC1 is reduced in the 73F9 mutant and nuclear-localized. "
  • Microscopy type: Light
  • Microscopy method: HA tag, N terminal FLAG tag
  • Strain: C1H
  • Gene model mapping comments: taken directly from publication
  • Localisation record: nucleus during tachyzoite