Toxoplasma gondii Protease TgSUB1 is Required for Cell Surface Processing of Micronemal Adhesive Complexes and Efficient Adhesion of Tachyzoites

Cell Microbiol. 2010 Jul 30. [Epub ahead of print]

Toxoplasma gondii Protease TgSUB1 is Required for Cell Surface Processing of Micronemal Adhesive Complexes and Efficient Adhesion of Tachyzoites

Lagal V, Binder EM, Huynh MH, Kafsack BF, Harris PK, Diez R, Chen D, Cole RN, Carruthers VB, Kim K.

Departments of Medicine and Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY 10461 USA.

Abstract
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 Deltasub1 parasites with TgSUB1 lacking the GPI anchor (Deltasub1::DeltaGPISUB1) only partially restores microneme protein processing. Loss of TgSUB1 decreases cell attachment and in vitro gliding efficiency leading to lower initial rates of invasion. Deltasub1 andDeltasub1::DeltaGPISUB1 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.

PMID: 20678172 [PubMed - as supplied by publisher]