Apical annuli are specialised sites of post-invasion secretion of dense granules in Toxoplasma

Abstract

Apicomplexans are ubiquitous intracellular parasites of animals. These parasites use a programmed sequence of secretory events to find, invade, and then reengineer their host cells to enable parasite growth and proliferation. The secretory organelles micronemes and rhoptries mediate the first steps of invasion. Both secrete their contents through the apical complex which provides an apical opening in the parasite's elaborate inner membrane complex (IMC) - an extensive subpellicular system of flattened membrane cisternae and proteinaceous meshwork that otherwise limits access of the cytoplasm to the plasma membrane for material exchange with the cell exterior. After invasion, a second secretion programme drives host cell remodelling and occurs from dense granules. The site(s) of dense granule exocytosis, however, has been unknown. In Toxoplasma gondii, small subapical annular structures that are embedded in the IMC have been observed, but the role or significance of these apical annuli to plasma membrane function has also been unknown. Here, we determined that integral membrane proteins of the plasma membrane occur specifically at these apical annular sites, that these proteins include SNARE proteins, and that the apical annuli are sites of vesicle fusion and exocytosis. Specifically, we show that dense granules require these structures for the secretion of their cargo proteins. When secretion is perturbed at the apical annuli, parasite growth is strongly impaired. The apical annuli, therefore, represent a second type of IMC-embedded structure to the apical complex that is specialised for protein secretion, and reveal that in Toxoplasma there is a physical separation of the processes of pre- and post-invasion secretion that mediate host-parasite interactions.

Data availability

Raw LC-MS data and PD search results have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD034193 and PXD044588.

The following data sets were generated

Article and author information

Author details

  1. Sara Chelaghma

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0009-0004-1832-4406
  2. Huiling Ke

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Konstantin Barylyuk

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3580-0345
  4. Thomas Krueger

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Ludek Koreny

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    lk360@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9979-3172
  6. Ross F Waller

    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    rfw26@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6961-9344

Funding

Wellcome Trust (214298_Z_18_Z)

  • Sara Chelaghma

Gordon and Betty Moore Foundation (7872)

  • Thomas Krueger

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Malcolm J McConville, The University of Melbourne, Australia

Version history

  1. Preprint posted: July 27, 2023 (view preprint)
  2. Received: November 15, 2023
  3. Accepted: December 5, 2023
  4. Accepted Manuscript published: January 25, 2024 (version 1)
  5. Version of Record published: February 9, 2024 (version 2)

Copyright

© 2024, Chelaghma et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Sara Chelaghma
  2. Huiling Ke
  3. Konstantin Barylyuk
  4. Thomas Krueger
  5. Ludek Koreny
  6. Ross F Waller
(2024)
Apical annuli are specialised sites of post-invasion secretion of dense granules in Toxoplasma
eLife 13:e94201.
https://doi.org/10.7554/eLife.94201

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https://doi.org/10.7554/eLife.94201

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