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

Venugopal, K. et al. (2017) Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry and microneme proteins and in parasite division. PLoS Pathogens, 13(4), e1006331. (doi: 10.1371/journal.ppat.1006331) (PMID:28430827) (PMCID:PMC5415223)

Abstract

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.

• Item Type: Articles
• Additional Information: KV, FS, MAH, GL, and SM are supported by the Laboratoire d’Excellence (LabEx) ParaFrap from the National Agency for Research ANR-11-LABX-0024 and ANR-14-CE14-0002-01. MAH is supported by the European Research Council (ERC Consolidator grant no. 614880). SM is supported by a Chaire d’Excellence Université Lille Nord de France/Centre National de la Recherche Scientifique (CNRS).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Venugopal, Dr Kannan
• Authors: Venugopal, K., Werkmeister, E., Barois, N., Saliou, J.-M., Poncet, A., Huot, L., Sindikubwabo, F., Hakimi, M. A., Langsley, G., Lafont, F., and Marion, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Pathogens
• Publisher: Public Library of Science
• ISSN: 1553-7366
• ISSN (Online): 1553-7374
• Copyright Holders: Copyright © 2017 Venugopal et al.
• First Published: First published in PLoS Pathogens 13(4): e1006331
• Publisher Policy: Reproduced under a Creative Commons License