Open AccessToxoplasma gondii protease TgSUB1 is required for cell surface processing of micronemal adhesive complexes and efficient adhesion of tachyzoites
Author(s) -
Lagal Vanessa,
Binder Emily M.,
Huynh MyHang,
Kafsack Bjorn F. C.,
Harris Philippa K.,
Diez Roberto,
Chen Dawn,
Cole Robert N.,
Carruthers Vern B.,
Kim Kami
Publication year - 2010
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2010.01509.x
Subject(s) - microneme , biology , toxoplasma gondii , microbiology and biotechnology , secretion , proteases , complementation , protease , cell adhesion , cell , biochemistry , apicomplexa , immunology , phenotype , antibody , plasmodium falciparum , malaria , gene , enzyme
Summary 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 Δ sub1 parasites with TgSUB1 lacking the GPI anchor (Δ sub1 ::Δ GPISUB1 ) only partially restores microneme protein processing. Loss of TgSUB1 decreases cell attachment and in vitro gliding efficiency leading to lower initial rates of invasion. Δ sub1 and Δ sub1 ::Δ GPISUB1 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.