Toxoplasma effector TgROP1 establishes membrane contact sites with the endoplasmic reticulum during infection

Membrane contact sites (MCS) are essential for organelle communication in eukaryotic cells. Pathogens also establish MCS with host organelles, but the mechanisms underlying these interactions and their role in infection remain poorly understood. Here, using a fluorescence sensor and CRISPR-based loss-of-function screening, together with imaging and proteomics, we identify the parasite effector mediating MCS between host endoplasmic reticulum (ER) and the vacuole containing the intracellular parasite Toxoplasma gondii. TgROP1 acts as a tether and mimics a canonical FFAT motif to bind the host ER proteins VAPA and VAPB. The loss of VAPA/B abolished host ER-Toxoplasma MCS and decreased pathogen growth. These findings indicate that targeting of host MCS tethers is a strategy exploited by pathogens during infection, which could inform future treatment design.

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Publication Details

Journal
Nature Microbiology
Published
2025-11-25
DOI
https://doi.org/10.1038/s41564-025-02193-3
Citations
3
Primary Topic
Toxoplasma gondii Research Studies
Type
article
Field-Weighted Citation Impact
6.14
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article

Toxoplasma effector TgROP1 establishes membrane contact sites with the endoplasmic reticulum during infection

Lena Pernas, Steffen Lawo, Chahat Mehra, Tania Medeiros et al.
3 citations
Nature Microbiology
Toxoplasma gondii Research Studies
6.14
article

Toxoplasma effector TgROP1 establishes membrane contact sites with the endoplasmic reticulum during infection

Lena Pernas, Steffen Lawo, Chahat Mehra, Tania Medeiros, Peter John Bradley, Katja Luck, Ana Catarina Matias, Julian Straub, Jesús Alvarado-Valverde, Francesca Torelli, Moritz Treeck, James D. Asaki
article en
3 citations

Abstract

Membrane contact sites (MCS) are essential for organelle communication in eukaryotic cells. Pathogens also establish MCS with host organelles, but the mechanisms underlying these interactions and their role in infection remain poorly understood. Here, using a fluorescence sensor and CRISPR-based loss-of-function screening, together with imaging and proteomics, we identify the parasite effector mediating MCS between host endoplasmic reticulum (ER) and the vacuole containing the intracellular parasite Toxoplasma gondii. TgROP1 acts as a tether and mimics a canonical FFAT motif to bind the host ER proteins VAPA and VAPB. The loss of VAPA/B abolished host ER-Toxoplasma MCS and decreased pathogen growth. These findings indicate that targeting of host MCS tethers is a strategy exploited by pathogens during infection, which could inform future treatment design.

Nature MicrobiologyVol. 10(12)
Howard Hughes Medical Institute (US), University of California, Los Angeles (US), The Francis Crick Institute (GB), Max Planck Institute for Biology of Ageing (DE), Institute of Molecular Biology (DE), Instituto Gulbenkian de Ciência (PT)
Openalex Percentile: Top 3%
Toxoplasma gondii Research Studies
6.14
DOIOpen Access PDFOpenAlex
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