Oligopeptidase B-dependent signaling mediates host cell invasion by Trypanosoma cruzi
- PMID: 9724634
- PMCID: PMC1170826
- DOI: 10.1093/emboj/17.17.4975
Oligopeptidase B-dependent signaling mediates host cell invasion by Trypanosoma cruzi
Abstract
Mammalian cell invasion by the intracellular protozoan parasite Trypanosoma cruzi is mediated by recruitment and fusion of host cell lysosomes, an unusual process that has been proposed to be dependent on the ability of parasites to trigger intracellular free calcium concentration ([Ca2+]i) transients in host cells. Previous work implicated the T.cruzi serine hydrolase oligopeptidase B in the generation of Ca2+-signaling activity in parasite extracts. Here we show that deletion of the gene encoding oligopeptidase B results in a marked defect in host cell invasion and in the establishment of infections in mice. The invasion defect is associated with the inability of oligopeptidase B null mutant trypomastigotes to mobilize Ca2+ from thapsigargin-sensitive stores in mammalian cells. Exogenous recombinant oligopeptidase B reconstitutes the oligopeptidase B-dependent Ca2+ signaling activity in null mutant parasite extracts, demonstrating that this enzyme is responsible for the generation of a signaling agonist for mammalian cells.
Similar articles
-
A cytosolic serine endopeptidase from Trypanosoma cruzi is required for the generation of Ca2+ signaling in mammalian cells.J Cell Biol. 1997 Feb 10;136(3):609-20. doi: 10.1083/jcb.136.3.609. J Cell Biol. 1997. PMID: 9024691 Free PMC article.
-
Dual role of signaling pathways leading to Ca(2+) and cyclic AMP elevation in host cell invasion by Trypanosoma cruzi.Infect Immun. 2000 Dec;68(12):6602-10. doi: 10.1128/IAI.68.12.6602-6610.2000. Infect Immun. 2000. PMID: 11083771 Free PMC article.
-
Trypanosoma cruzi: parasite and host cell signaling during the invasion process.Subcell Biochem. 2008;47:82-91. doi: 10.1007/978-0-387-78267-6_6. Subcell Biochem. 2008. PMID: 18512343 Review.
-
Trypanosoma brucei brucei oligopeptidase B null mutants display increased prolyl oligopeptidase-like activity.Mol Biochem Parasitol. 2012 Mar-Apr;182(1-2):7-16. doi: 10.1016/j.molbiopara.2011.11.007. Epub 2011 Nov 22. Mol Biochem Parasitol. 2012. PMID: 22123425
-
Molecular basis of mammalian cell invasion by Trypanosoma cruzi.An Acad Bras Cienc. 2006 Mar;78(1):87-111. doi: 10.1590/s0001-37652006000100010. Epub 2006 Mar 8. An Acad Bras Cienc. 2006. PMID: 16532210 Review.
Cited by
-
Impairment of infectivity and immunoprotective effect of a LYT1 null mutant of Trypanosoma cruzi.Infect Immun. 2008 Jan;76(1):443-51. doi: 10.1128/IAI.00400-07. Epub 2007 Oct 15. Infect Immun. 2008. PMID: 17938222 Free PMC article.
-
Oligopeptidase B from Leishmania amazonensis: molecular cloning, gene expression analysis and molecular model.Parasitol Res. 2007 Sep;101(4):865-75. doi: 10.1007/s00436-007-0630-8. Parasitol Res. 2007. PMID: 18074461
-
Parasite prolyl oligopeptidases and the challenge of designing chemotherapeuticals for Chagas disease, leishmaniasis and African trypanosomiasis.Curr Med Chem. 2013;20(25):3103-15. doi: 10.2174/0929867311320250006. Curr Med Chem. 2013. PMID: 23514419 Free PMC article. Review.
-
RNA-seq-based metatranscriptomic and microscopic investigation reveals novel metalloproteases of Neobodo sp. as potential virulence factors for soft tunic syndrome in Halocynthia roretzi.PLoS One. 2012;7(12):e52379. doi: 10.1371/journal.pone.0052379. Epub 2012 Dec 27. PLoS One. 2012. PMID: 23300657 Free PMC article.
-
Cell signaling during Trypanosoma cruzi invasion.Front Immunol. 2012 Nov 28;3:361. doi: 10.3389/fimmu.2012.00361. eCollection 2012. Front Immunol. 2012. PMID: 23230440 Free PMC article.
References
Publication types
MeSH terms
Substances
Associated data
- Actions
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous