Toxoplasma gondii HOOK-FTS-HIP complex is critical for secretory organelle discharge during motility, invasion, and egress

Dubois, D. J., Chehade, S., Marq, J.-B., Venugopal, K. , Maco, B., Puig, A. T. I., Soldati-Favre, D. and Marion, S. (2023) Toxoplasma gondii HOOK-FTS-HIP complex is critical for secretory organelle discharge during motility, invasion, and egress. mBio, 14(3), (doi: 10.1128/mbio.00458-23) (PMID:37093045) (PMCID:PMC10294612)

[img] Text
297704.pdf - Published Version
Available under License Creative Commons Attribution.

4MB

Abstract

Members of the Apicomplexa phylum possess specialized secretory organelles that discharge, apically and in a timely regulated manner, key factors implicated in parasite motility, host cell invasion, egress and subversion of host cellular functions. The mechanisms regulating trafficking and apical docking of these secretory organelles are only partially elucidated. Here, we characterized two conserved endosomal trafficking regulators known to promote vesicle transport and/or fusion, HOOK and Fused Toes (FTS), in the context of organelle discharge in Toxoplasma gondii. TgHOOK and TgFTS form a complex with a coccidian-specific partner, named HOOK interacting partner (HIP). TgHOOK displays an apically enriched vesicular pattern and concentrates at the parasite apical tip where it colocalizes with TgFTS and TgHIP. Functional investigations revealed that TgHOOK is dispensable but fitness conferring. The protein regulates the apical positioning and secretion of micronemes and contributes to egress, motility, host cell attachment, and invasion. Conditional depletion of TgFTS or TgHIP impacted on the same processes but led to more severe phenotypes. This study provides evidence of endosomal trafficking regulators involved in the apical exocytosis of micronemes and possibly as a consequence or directly on the discharge of the rhoptries.

Item Type:Articles
Additional Information:This research was supported by Swiss National Science Foundation (FN310030B_166678 to D.S.-F.) and by Scientific and Technological Cooperation Program Switzerland—Rio de Janeiro (STCPSRJ) to Karine Frenal (IZRJZ3_164183). B.M. was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program under grant agreement 695596.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Venugopal, Dr Kannan
Creator Roles:
Venugopal, K.Methodology
Authors: Dubois, D. J., Chehade, S., Marq, J.-B., Venugopal, K., Maco, B., Puig, A. T. I., Soldati-Favre, D., and Marion, S.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:mBio
Publisher:American Society for Microbiology
ISSN:2150-7511
ISSN (Online):2150-7511
Published Online:24 April 2023
Copyright Holders:Copyright © 2023 Dubois et al.
First Published:First published in mBio 14(3)
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record