The cathepsin B of Toxoplasma gondii, toxopain-1, is critical for parasite invasion and rhoptry protein processing

Xuchu Que, Huân Ngô, Jeffrey Lawton, Mary Gray, Qing Liu, Juan Engel, Linda Brinen, Partho Ghosh, Keith A. Joiner, Sharon L. Reed

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Cysteine proteinases play a major role in invasion and intracellular survival of a number of pathogenic parasites. We cloned a single copy gene, tgcpl, from Toxoplasma gondii and refolded recombinant enzyme to yield active proteinase. Substrate specificity of the enzyme and homology modeling identified the proteinase as a cathepsin B. Specific cysteine proteinase inhibitors interrupted invasion by tachyzoites. The T. gondii cathepsin B localized to rhoptries, secretory organelles required for parasite invasion into cells. Processing of the pro-rhoptry protein 2 to mature rhoptry proteins was delayed by incubation of extracellular parasites with a cathepsin B inhibitor prior to pulse-chase immunoprecipitation. Delivery of cathepsin B to mature rhoptries was impaired in organisms with disruptions in rhoptry formation by expression of a dominant negative μ1-adaptin. Similar disruption of rhoptry formation was observed when infected fibroblasts were treated with a specific inhibitor of cathepsin B, generating small and poorly developed rhoptries. This first evidence for localization of a cysteine proteinase to the unusual rhoptry secretory organelle of an apicomplexan parasite suggests that the rhoptries may be a prototype of a lysosome-related organelle and provides a critical link between cysteine proteinases and parasite invasion for this class of organism.

Original languageEnglish (US)
Pages (from-to)25791-25797
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number28
DOIs
StatePublished - Jul 12 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Que, X., Ngô, H., Lawton, J., Gray, M., Liu, Q., Engel, J., Brinen, L., Ghosh, P., Joiner, K. A., & Reed, S. L. (2002). The cathepsin B of Toxoplasma gondii, toxopain-1, is critical for parasite invasion and rhoptry protein processing. Journal of Biological Chemistry, 277(28), 25791-25797. https://doi.org/10.1074/jbc.M202659200