Universität zu Köln

Hermanns, Thomas ORCID: 0000-0001-5350-7479, Mueller, Urs B., Koenen-Waisman, Stephanie, Howard, Jonathan C. and Steinfeldt, Tobias (2016). The Toxoplasma gondii rhoptry protein ROP18 is an Irga6-specific kinase and regulated by the dense granule protein GRA7. Cell Microbiol., 18 (2). S. 244 - 260. HOBOKEN: WILEY. ISSN 1462-5822

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Abstract

In mice, avirulent strains (e. g. types II and III) of the protozoan parasite Toxoplasma gondii are restricted by the immunity-related GTPase (IRG) resistance system. Loading of IRG proteins onto the parasitophorous vacuolar membrane (PVM) is required for vacuolar rupture resulting in parasite clearance. In virulent strain (e. g. type I) infections, polymorphic effector proteins ROP5 and ROP18 cooperate to phosphorylate and thereby inactivate mouse IRG proteins to preserve PVM integrity. In this study, we confirmed the dense granule protein GRA7 as an additional component of the ROP5/ROP18 kinase complex and identified GRA7 association with the PVM by direct binding to ROP5. The absence of GRA7 results in reduced phosphorylation of Irga6 correlated with increased vacuolar IRG protein amounts and attenuated virulence. Earlier work identified additional IRG proteins as targets of T. gondii ROP18 kinase. We show that the only specific target of ROP18 among IRG proteins is in fact Irga6. Similarly, we demonstrate that GRA7 is strictly an Irga6-specific virulence effector. This identifies T. gondii GRA7 as a regulator for ROP18-specific inactivation of Irga6. The structural diversity of the IRG proteins implies that certain family members constitute additional specific targets for other yet unknown T. gondii virulence effectors.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hermanns, Thomas UNSPECIFIED orcid.org/0000-0001-5350-7479 UNSPECIFIED Mueller, Urs B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koenen-Waisman, Stephanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Howard, Jonathan C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Steinfeldt, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-286157
DOI:	10.1111/cmi.12499
Journal or Publication Title:	Cell Microbiol.
Volume:	18
Number:	2
Page Range:	S. 244 - 260
Date:	2016
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1462-5822
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IMMUNITY-RELATED GTPASES; IRG RESISTANCE GTPASES; HOST-RESISTANCE; ACUTE VIRULENCE; IFN-GAMMA; INTRACELLULAR PATHOGENS; PSEUDOKINASE ROP5; CELLULAR-RESPONSE; GENE-EXPRESSION; FAMILY Multiple languages Cell Biology; Microbiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28615