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.

Nature Microbiology
|October 10, 2025
PubMed

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 II01:27

Diversity of Protists II

Alveolates are a group of organisms recognized by the presence of alveoli, which are cytoplasmic sacs located beneath the cell membrane. While their function remains uncertain, alveoli may help regulate water balance by controlling how much water enters and leaves the cell. In dinoflagellates, these structures may serve as armor plates. There are three major types of alveolates: ciliates, which move using cilia; dinoflagellates, which use flagella for movement; and apicomplexans, which are...
781
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
4.7K
Diversity of Protists I01:15

Diversity of Protists I

Excavata is a diverse group of protists that includes both chemoorganotrophic and phototrophic species, with some thriving in anaerobic environments. Among the key groups within Excavata are diplomonads and parabasalids, which are flagellated protists that lack mitochondria and chloroplasts. These microorganisms typically inhabit anoxic environments, such as the intestines of animals, where they exist either symbiotically or as parasites, relying on fermentation for energy production. Some...
850
Coat Assembly and GTPases01:33

Coat Assembly and GTPases

Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
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...
4.2K
Symbiosis00:58

Symbiosis

Symbiotic relationships are long-term, close interactions between individuals of different species that affect the distribution and abundance of those species. When a relationship is beneficial to both species, this is called mutualism. When the relationship is beneficial to one species but neither beneficial nor harmful to the other species, this is called commensalism. When one organism is harmed to benefit another, the relationship is known as parasitism. These types of relationships often...
36.9K
Vesicular Tubular Clusters01:45

Vesicular Tubular Clusters

After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
3.1K