Toxoplasma gondii VIP1 mediates parasitophorous vacuole-host endoplasmic reticulum interactions to facilitate
Julia D Romano1, Ruth Buh2, Tanner Grudda2
1Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA. jromano2@jhu.edu.
Abstract:
Membrane contact sites (MCS) are areas of close apposition between organelles without membrane fusion, allowing for exchange of biomolecules. The endoplasmic reticulum (ER) forms many MCS via two proteins, vesicle-associated membrane protein-associated proteins A and B (VAPA and VAPB). The obligate intracellular parasite Toxoplasma gondii resides within mammalian cells in a parasitophorous vacuole (PV), which closely contacts the host ER at distances compatible with MCS. However, the proteins mediating this interaction remain largely unknown. Here, using molecular and microscopy approaches, we show that VAPA and VAPB localize at the PV membrane and, with motile sperm domain-containing protein 2 (MOSPD2), mediate ER-PV interactions. Cells deficient in VAPA, VAPB and MOSPD2 do not recruit host ER at the PV, and parasites show growth defects. We identify a parasite protein that localizes at the PV membrane, called TgVIP1, which harbours an FFAT-like motif that binds VAPA and VAPB. These findings lay the basis for understanding how and why Toxoplasma exploits ER-PV interactions and may uncover new drug targets.
Insights
Toxoplasma gondii parasites exploit host cell endoplasmic reticulum (ER) interactions via specific proteins. This study identifies key proteins mediating these membrane contact sites (MCS), revealing potential drug targets.
Area of Science:
- Cell Biology
- Parasitology
- Molecular Biology
Background:
- Membrane contact sites (MCS) facilitate inter-organelle communication without fusion.
- The endoplasmic reticulum (ER) interacts with various organelles via proteins like VAPA and VAPB.
- Toxoplasma gondii forms a parasitophorous vacuole (PV) that contacts the host ER, but mediating proteins are unknown.
Purpose of the Study:
- To identify proteins mediating ER-PV interactions in Toxoplasma gondii.
- To understand the role of these proteins in parasite growth and ER recruitment.
Main Methods:
- Molecular biology techniques
- Microscopy approaches
- Analysis of protein localization and function in deficient cells
Main Results:
- VAPA and VAPB localize to the PV membrane and mediate ER-PV contact with MOSPD2.
- Deficiency in VAPA, VAPB, and MOSPD2 impairs ER recruitment to the PV and causes parasite growth defects.
- A novel parasite protein, TgVIP1, with an FFAT-like motif binds VAPA and VAPB.
Conclusions:
- VAPA, VAPB, and MOSPD2 are crucial for ER-PV membrane contact sites in Toxoplasma gondii.
- TgVIP1 mediates the interaction between the parasite PV and the host ER.
- These findings offer insights into parasite-host interactions and potential therapeutic strategies.
Related Concept Videos
Diversity of Protists II
Intralumenal Vesicles and Multivesicular Bodies
Diversity of Protists I
Coat Assembly and GTPases
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Symbiosis
Vesicular Tubular Clusters
With the help of motor proteins such...


