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Toxoplasma gondii protease TgSUB1 is required for cell surface processing of micronemal adhesive complexes and efficient adhesion of tachyzoites.

TitleToxoplasma gondii protease TgSUB1 is required for cell surface processing of micronemal adhesive complexes and efficient adhesion of tachyzoites.
Publication TypeJournal Article
Year of Publication2010
AuthorsLagal V, Binder EM, Huynh M-H, Kafsack BFC, Harris PK, Diez R, Chen D, Cole RN, Carruthers VB, Kim K
JournalCell Microbiol
Volume12
Issue12
Pagination1792-808
Date Published2010 Dec
ISSN1462-5822
KeywordsAnimals, Cell Adhesion, Cell Adhesion Molecules, Cells, Cultured, Disease Models, Animal, Gene Deletion, Genetic Complementation Test, Humans, Locomotion, Membrane Proteins, Mice, Protozoan Proteins, Subtilisins, Toxoplasma, Toxoplasmosis, Animal, Virulence, Virulence Factors
Abstract

Host cell invasion by Toxoplasma gondii is critically dependent upon adhesive proteins secreted from the micronemes. Proteolytic trimming of microneme contents occurs rapidly after their secretion onto the parasite surface and is proposed to regulate adhesive complex activation to enhance binding to host cell receptors. However, the proteases responsible and their exact function are still unknown. In this report, we show that T. gondii tachyzoites lacking the microneme subtilisin protease TgSUB1 have a profound defect in surface processing of secreted microneme proteins. Notably parasites lack protease activity responsible for proteolytic trimming of MIC2, MIC4 and M2AP after release onto the parasite surface. Although complementation with full-length TgSUB1 restores processing, complementation of Δsub1 parasites with TgSUB1 lacking the GPI anchor (Δsub1::ΔGPISUB1) only partially restores microneme protein processing. Loss of TgSUB1 decreases cell attachment and in vitro gliding efficiency leading to lower initial rates of invasion. Δsub1 and Δsub1::ΔGPISUB1 parasites are also less virulent in mice. Thus TgSUB1 is involved in micronemal protein processing and regulation of adhesive properties of macromolecular adhesive complexes involved in host cell invasion.

DOI10.1111/j.1462-5822.2010.01509.x
Alternate JournalCell Microbiol
PubMed ID20678172
PubMed Central IDPMC2997387
Grant ListR01 AI046675 / AI / NIAID NIH HHS / United States
R01 AI046985-09 / AI / NIAID NIH HHS / United States
R01 AI046675-11 / AI / NIAID NIH HHS / United States
R01 AI046985 / AI / NIAID NIH HHS / United States
R01 AI46985 / AI / NIAID NIH HHS / United States
5T32-A107506 / / PHS HHS / United States

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