Toxoplasma effector TgROP1 establishes membrane contact sites with the endoplasmic reticulum during infection
Year: 2025
Type: article
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.
Source: Nature Microbiology
Authors: Chahat Mehra, Jesús Alvarado Valverde, Ana Margarida Nogueira Matias, Francesca Torelli, Tânia Catarina Medeiros, Julian Straub, James D. Asaki, Peter J. Bradley, Katja Luck, Steffen Lawo, Moritz Treeck, Lena Pernas
Language: English
Subfield: Parasitology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Awards: A systems-biology approach to identify Toxoplasma effectors that co-opt host cell transcription and their function in immune system suppression., G3800879736, G4727776248, SFB 1218: Regulation der zellulären Funktion durch Mitochondrien, G6526953788, G683095315, G7518760545, G7936340974, G895578454, G9000110411
OpenAlex ID: W4416673704