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Distinct contribution of Toxoplasma gondii rhomboid proteases 4 and 5 to micronemal protein protease 1 activity during invasion

Guérin, Amandine
Lebrun, Maryse
Published in Molecular Microbiology. 2015, vol. 97, no. 2, p. 244-62
Abstract Host cell entry by the Apicomplexa is associated with the sequential secretion of invasion factors from specialized apical organelles. Secretion of micronemal proteins (MICs) complexes by Toxoplasma gondii facilitates parasite gliding motility, host cell attachment and entry, as well as egress from infected cells. The shedding of MICs during these steps is mediated by micronemal protein proteases MPP1, MPP2 and MPP3. The constitutive activity of MPP1 leads to the cleavage of transmembrane MICs and is linked to the surface rhomboid protease 4 (ROM4) and possibly to rhomboid protease 5 (ROM5). To determine their importance and respective contribution to MPP1 activity, in this study ROM4 and ROM5 genes were abrogated using Cre-recombinase and CRISPR-Cas9 nuclease, respectively, and shown to be dispensable for parasite survival. Parasites lacking ROM4 predominantly engage in twirling motility and exhibit enhanced attachment and impaired invasion, whereas intracellular growth and egress is not affected. The substrates MIC2 and MIC6 are not cleaved in rom4-ko parasites, in contrast, intramembrane cleavage of AMA1 is reduced but not completely abolished. Shedding of MICs and invasion are not altered in the absence of ROM5; however, this protease responsible for the residual cleavage of AMA1 is able to cleave other AMA family members and exhibits a detectable contribution to invasion in the absence of ROM4.
PMID: 25846828
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Article (Published version) (20.8 MB) - document accessible for UNIGE members only Limited access to UNIGE
Research group Biologie d'un parasite intracellulaire obligatoire (773)
Swiss National Science Foundation: FN3100A0-116722
European Commission: EVIMALAR
(ISO format)
RUGARABAMU, George et al. Distinct contribution of Toxoplasma gondii rhomboid proteases 4 and 5 to micronemal protein protease 1 activity during invasion. In: Molecular microbiology, 2015, vol. 97, n° 2, p. 244-62. doi: 10.1111/mmi.13021 https://archive-ouverte.unige.ch/unige:74110

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Deposited on : 2015-07-14

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