ROP18 Is a Rhoptry Kinase Controlling the Intracellular Proliferation of Toxoplasma gondii

PLoS Pathogens

Jean François Dubremetz¹  Stefan T Arold¹  Henri Vial²  Hiba El Hajj³  Gilles Labesse³  Maryse Lebrun³ 

[1] Centre de Biochimie Structurale, Centre National de la Recherche Scientifique, Université Montpellier 1, Montpellier, France;Centre de Biochimie Structurale, Institut National de la Santé et de la Recherche Médicale, Montpellier, France;UMR 5539, Centre National de la Recherche Scientifique, Université de Montpellier 2, Montpellier, France

关键词: Parasitic diseases;    Tachyzoites;    Sequence motif analysis;    Host cells;    Toxoplasma gondii;    Recombinant proteins;    Membrane proteins;    Parasite replication;   

DOI  :  10.1371/journal.ppat.0030014

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Toxoplasma gondii is an obligate intracellular parasite for which the discharge of apical organelles named rhoptries is a key event in host cell invasion. Among rhoptry proteins, ROP2, which is the prototype of a large protein family, is translocated in the parasitophorous vacuole membrane during invasion. The ROP2 family members are related to protein-kinases, but only some of them are predicted to be catalytically active, and none of the latter has been characterized so far. We show here that ROP18, a member of the ROP2 family, is located in the rhoptries and re-localises at the parasitophorous vacuole membrane during invasion. We demonstrate that a recombinant ROP18 catalytic domain (amino acids 243–539) possesses a protein-kinase activity and phosphorylate parasitic substrates, especially a 70-kDa protein of tachyzoites. Furthermore, we show that overexpression of ROP18 in transgenic parasites causes a dramatic increase in intra-vacuolar parasite multiplication rate, which is correlated with kinase activity. Therefore, we demonstrate, to our knowledge for the first time, that rhoptries can discharge active protein-kinases upon host cell invasion, which can exert a long-lasting effect on intracellular parasite development and virulence.

【 授权许可】

CC BY