Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication

Venugopal, K. et al. (2020) Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication. PLoS Pathogens, 16(5), e1008106. (doi: 10.1371/journal.ppat.1008106) (PMID:32463830) (PMCID:PMC7255593)

Abstract

Toxoplasma gondii possesses an armada of secreted virulent factors that enable parasite invasion and survival into host cells. These factors are contained in specific secretory organelles, the rhoptries, micronemes and dense granules that release their content upon host cell recognition. Dense granules are secreted in a constitutive manner during parasite replication and play a crucial role in modulating host metabolic and immune responses. While the molecular mechanisms triggering rhoptry and microneme release upon host cell adhesion have been well studied, constitutive secretion remains a poorly explored aspect of T. gondii vesicular trafficking. Here, we investigated the role of the small GTPase Rab11A, a known regulator of exocytosis in eukaryotic cells. Our data revealed an essential role of Rab11A in promoting the cytoskeleton driven transport of dense granules and the release of their content into the vacuolar space. Rab11A also regulates transmembrane protein trafficking and localization during parasite replication, indicating a broader role of Rab11A in cargo exocytosis at the plasma membrane. Moreover, we found that Rab11A also regulates extracellular parasite motility and adhesion to host cells. In line with these findings, MIC2 secretion was altered in Rab11A-defective parasites, which also exhibited severe morphological defects. Strikingly, by live imaging we observed a polarized accumulation of Rab11A-positive vesicles and dense granules at the apical pole of extracellular motile and invading parasites suggesting that apically polarized Rab11A-dependent delivery of cargo regulates early secretory events during parasite entry into host cells.

• Item Type: Articles
• Additional Information: KV, SM and GL have been supported by the Laboratoire d’Excellence (LabEx) ParaFrap from the National Agency for Research ANR-11-LABX-0024 grant and by the ANR-14-CE14-0002-01 grant. SM has been supported by a joint Chaire d’Excellence from Université of Lille and the Centre National pour la Recherche Scientifique (CNRS).
• Keywords: Toxoplasma , Rab11A, apicomplexa, secretion, trafficking.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Periz, Dr Javier and Meissner, Professor Markus and Venugopal, Dr Kannan

Creator Roles

Venugopal, K.: Conceptualization, Formal analysis, Investigation, Methodology, Writing – original draft
Periz, J.: Methodology
Meissner, M.: Investigation, Methodology, Writing – review and editing

• Authors: Venugopal, K., Chehade, S., Werkmeister, E., Bariois, N., Periz, J., Lafont, F., Tardieux, I., Khalife, J., Langsley, G., Meissner, M., and Marion, S.
• Subjects: Q Science > QR Microbiology
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Pathogens
• Journal Abbr.: PLoS Pathog.
• Publisher: Public Library of Science
• ISSN: 1553-7366
• ISSN (Online): 1553-7374
• Published Online: 28 May 2020
• Copyright Holders: Copyright © 2020 Venugopal et al.
• First Published: First published in PLoS Pathogens 16(5): e1008106
• Publisher Policy: Reproduced under a Creative Commons License