Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry and microneme proteins and in parasite division

PLoS Pathogens

Frank Lafont¹  Anais Poncet¹  Kannan Venugopal¹  Jean-Michel Saliou¹  Sabrina Marion¹  Elisabeth Werkmeister¹  Ludovic Huot¹  Nicolas Barois¹  Mohamed Ali Hakimi²  Fabien Sindikubwabo²  Gordon Langsley³ 

[1] Centre d'Infection et d'Immunité de Lille, Université de Lille, Inserm U1019, CNRS UMR 8204, CHU Lille, Institut Pasteur de Lille, Lille, France;IAB, Team Host-pathogen interactions & immunity to infection, Université Grenoble Alpes, Inserm U1209, CNRS UMR5309, Grenoble, France;Laboratoire de Biologie Cellulaire Comparative des Apicomplexes, Faculté de Médicine, Université Paris Descartes—Sorbonne Paris Cité, France. Inserm U1016, CNRS UMR8104, Institut Cochin, Paris, France

关键词: Parasite replication;    Vacuoles;    Toxoplasma gondii;    Vesicles;    Cell cycle;    cell division;    Cellular structures;    organelles;    Parasitic cell cycles;    Membrane proteins;   

DOI  :  10.1371/journal.ppat.1006331

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Toxoplasma gondii possesses a highly polarized secretory system, which efficiently assembles de novo micronemes and rhoptries during parasite replication. These apical secretory organelles release their contents into host cells promoting parasite invasion and survival. Using a CreLox-based inducible knock-out strategy and the ddFKBP over-expression system, we unraveled novel functions of the clathrin adaptor complex TgAP1. First, our data indicate that AP1 in T. gondii likely functions as a conserved heterotetrameric complex composed of the four subunits γ, β, μ1, σ1 and interacts with known regulators of clathrin-mediated vesicular budding such as the unique ENTH-domain containing protein, which we named Epsin-like protein (TgEpsL). Disruption of the μ1 subunit resulted in the mis-sorting of microneme proteins at the level of the Trans-Golgi-Network (TGN). Furthermore, we demonstrated that TgAP1 regulates rhoptry biogenesis by activating rhoptry protein exit from the TGN, but also participates in the post-Golgi maturation process of preROP compartments into apically anchored club-shaped mature organelles. For this latter activity, our data indicate a specific functional relationship between TgAP1 and the Rab5A-positive endosome-like compartment. In addition, we unraveled an original role for TgAP1 in the regulation of parasite division. APμ1-depleted parasites undergo normal daughter cell budding and basal complex assembly but fail to segregate at the end of cytokinesis.

【 授权许可】

CC BY