scholarly journals Toxoplasma gondii dense granule protein 15 induces apoptosis in choriocarcinoma JEG-3 cells through endoplasmic reticulum stress

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei Wei ◽  
Fangfang Zhang ◽  
He Chen ◽  
Yuanyuan Tang ◽  
Tian Xing ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Toxoplasma Gondii ◽  
Endoplasmic Reticulum Stress ◽  
Dense Granule ◽  
Granule Protein

Toxoplasma gondii dense granule protein 3 (GRA3) is a type I transmembrane protein that possesses a cytoplasmic dilysine (KKXX) endoplasmic reticulum (ER) retrieval motif

Parasitology ◽  
2005 ◽  
Vol 131 (2) ◽  
pp. 169-179 ◽  
Author(s):  
F. L. HENRIQUEZ ◽  
M. B. NICKDEL ◽  
R. MCLEOD ◽  
R. E. LYONS ◽  
K. LYONS ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Endoplasmic Reticulum ◽  
Toxoplasma Gondii ◽  
Transmembrane Domain ◽  
Neospora Caninum ◽  
Parasitophorous Vacuole ◽  
Dense Granule ◽  
Type I ◽  
Dense Granules ◽  
Granule Protein

Studies using antibodies to immunolocalize the Toxoplasma gondii dense granule protein GRA3, have shown that this protein associates strongly with the parasitophorous vacuole membrane (PVM). However, as there was no predicted membrane-spanning domain this highlighted an unanswered paradox. We demonstrate that the previously published sequence for GRA3 is actually an artificial chimera of 2 proteins. One protein, of molecular weight 65 kDa, shares the C-terminus with published GRA3 and possesses no significant sequence similarity with any protein thus far deposited in Genbank. The second, with a predicted molecular weight of 24 kDa shares the N-terminal region, is recognized by the monoclonal antibody 2H11 known to react with the dense granules of T. gondii and is therefore the authentic GRA3. The corrected GRA3 has an N-terminal secretory signal sequence and a transmembrane domain consistent with its insertion into the PVM. Antibodies to recombinant GRA3 recognize a protein of 24 kDa in T. gondii excretory–secretory antigen preparations. The signal peptide is necessary and sufficient to target GFP to the dense granules and parasitophorous vacuole. A homologue was identified in Neospora caninum. Finally, GRA3 possesses a dilysine ‘KKXX’ endoplasmic reticulum (ER) retrieval motif that rationalizes its association with PVM and possibly the host cell ER.

In vivo expression and distribution of dense granule protein 7 (GRA7) in the exoenteric (tachyzoite, bradyzoite) and enteric (coccidian) forms of Toxoplasma gondii

Parasitology ◽  
1999 ◽  
Vol 119 (3) ◽  
pp. 259-265 ◽  
Author(s):  
D. J. P. FERGUSON ◽  
D. JACOBS ◽  
E. SAMAN ◽  
J-F. DUBREMETZ ◽  
S. E. WRIGHT
Keyword(s):  
Toxoplasma Gondii ◽  
Staining Pattern ◽  
Parasitophorous Vacuole ◽  
Dense Granule ◽  
Parasite Development ◽  
Double Labelling ◽  
Granule Protein ◽  
Specific Variation ◽  
Strong Staining

The in vivo expression and distribution of the dense granule protein GRA7 was examined in both the exoenteric (tachyzoite and bradyzoite) and enteric (coccidian) forms of Toxoplasma gondii by immunocytochemistry. There was strong staining of GRA7 in granules within all the infectious stages (tachyzoite, bradyzoite, merozoite and sporozoite). During tachyzoite development, GRA7 was secreted and was associated with the parasitophorous vacuole. In contrast, although there was staining of granules within the bradyzoites of more mature cysts, there appeared to be little staining of the tissue cyst wall or host cell. The apparent stage-specific variation in secretion of GRA7 between tachyzoites and bradyzoites was confirmed by double labelling using stage-specific markers (SAG1 and BAG1). In the enteric forms in the cat gut there was strong labelling of the PV containing early asexual and sexual stages and staining of a few granules in the apical cytoplasm of the merozoite. The positive enteric staining pattern differentiates GRA7 from the other GRA proteins (GRA1–6) which were absent in the merozoites and enteric stages. The staining pattern of GRA7 with strong staining during tachyzoite and enteric development and reduced staining in the tissue cysts is similar to that seen for NTPases. The function of GRA7 is unknown but it is unique among the dense granule proteins in being expressed in all the infectious forms of T. gondii which would point to a basic role in the vacuolar adaptations required for active parasite development.

scholarly journals Dense granule protein, GRA64 interacts with host cell ESCRT proteins during Toxoplasma gondii infection

2021 ◽  
Author(s):  
Joshua Mayoral ◽  
Rebekah B. Guevara ◽  
Yolanda Rivera-Cuevas ◽  
Vincent Tu ◽  
Tadakimi Tomita ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Electron Tomography ◽  
Cell Activity ◽  
Dense Granule ◽  
Secreted Proteins ◽  
Toxoplasma Infection ◽  
Granule Protein ◽  
Novel Host ◽  
Toxoplasma Gondii Infection

The intracellular parasite Toxoplasma gondii adapts to diverse host cell environments within a replicative compartment that is heavily decorated by secreted proteins. In attempts to identify novel parasite secreted proteins that influence host cell activity, we identified and characterized a trans-membrane dense granule protein dubbed GRA64 (TGME49_202620). We found that GRA64 is on the parasitophorous vacuolar membrane (PVM) and is partially exposed to the host cell cytoplasm in both tachyzoite and bradyzoite parasitophorous vacuoles. Using co-immunoprecipitation and proximity-based biotinylation approaches, we demonstrate that GRA64 appears to interact with certain components of the host Endosomal Sorting Complexes Required for Transport (ESCRT). Genetic disruption of GRA64 does not affect acute Toxoplasma virulence in mice nor encystation as observed via tissue cyst burdens in mice during chronic infection. However, ultrastructural analysis of Dgra64 tissue cysts using electron tomography revealed enlarged vesicular structures underneath the cyst membrane, suggesting a role for GRA64 in organizing the recruitment of ESCRT proteins and subsequent intracystic vesicle formation. This study uncovers a novel host-parasite interaction that contributes to an emerging paradigm in which specific host ESCRT proteins are recruited to the limiting membranes (PVMs) of tachyzoite and bradyzoite vacuoles formed during acute and chronic Toxoplasma infection.

scholarly journals Reactive Oxygen Species-Triggered Trophoblast Apoptosis Is Initiated by Endoplasmic Reticulum Stress via Activation of Caspase-12, CHOP, and the JNK Pathway in Toxoplasma gondii Infection in Mice

2012 ◽  
Vol 80 (6) ◽  
pp. 2121-2132 ◽  
Author(s):  
Xiucai Xu ◽  
Tingting Liu ◽  
Aimei Zhang ◽  
Xingxing Huo ◽  
Qingli Luo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endoplasmic Reticulum ◽  
Toxoplasma Gondii ◽  
Endoplasmic Reticulum Stress ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Jnk Pathway ◽  
Content Type ◽  
Caspase 12

ABSTRACTToxoplasma gondiiinfection in pregnant women may result in abortion or in fetal teratogenesis; however, the underlying mechanisms are still unclear. In this paper, based on a murine model, we showed that maternal infection with RH strainT. gondiitachyzoites induced elevated production of reactive oxygen species (ROS), local oxidative stress, and subsequent apoptosis of placental trophoblasts. PCR array analysis of 84 oxidative stress-related genes demonstrated that 27 genes were upregulated at least 2-fold and that 9 genes were downregulated at least 2-fold in theT. gondiiinfection group compared with levels in the control group. The expression of NADPH oxidase 1 (Nox1) and glutathione peroxidase 6 (Gpx6) increased significantly, about 25-fold. The levels of malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) increased significantly withT. gondiiinfection, and levels of glutathione (GSH) decreased rapidly.T. gondiiinfection increased the early expression of endoplasmic reticulum stress (ERS) markers, followed by cleavage of caspase-12, activation of ASK1/JNK, and increased apoptosis of trophoblasts, bothin vivoandin vitro. The apoptosis of trophoblasts, the activation of caspase-12 and the ASK1/JNK pathway, and the production of peroxides were dramatically inhibited by pretreatment withN-acetylcysteine (NAC). The upregulation of Nox1 was contact dependent and preceded the increase in levels of ERS markers and the activation of the proapoptosis cascade. Thus, we concluded that apoptosis in placental trophoblasts was initiated predominantly by ROS-mediated ERS via activation of caspase-12, CHOP, and the JNK pathway in acuteT. gondiiinfection. Elevated ROS production is the central event inT. gondii-induced apoptosis of placental trophoblasts.

scholarly journals The amino-terminal region of dense granule protein 6 of Toxoplasma gondii stimulates IFN-γ production by microglia

2020 ◽  
Vol 22 (8) ◽  
pp. 375-378 ◽  
Author(s):  
Qila Sa ◽  
Corinne Mercier ◽  
Marie-France Cesbron-Delauw ◽  
Yasuhiro Suzuki
Keyword(s):  
Toxoplasma Gondii ◽  
Dense Granule ◽  
Terminal Region ◽  
Amino Terminal ◽  
Granule Protein ◽  
Ifn Γ

Characterization of strain-specific phenotypes associated with knockout of dense granule protein 9 in Toxoplasma gondii

2019 ◽  
Vol 229 ◽  
pp. 53-61 ◽  
Author(s):  
Huanping Guo ◽  
Yang Gao ◽  
Honglin Jia ◽  
Paul Franck Adjou Moumouni ◽  
Tatsunori Masatani ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Dense Granule ◽  
Granule Protein

scholarly journals Strain-specific activation of the NF-κB pathway by GRA15, a novel Toxoplasma gondii dense granule protein

2011 ◽  
Vol 208 (1) ◽  
pp. 195-212 ◽  
Author(s):  
Emily E. Rosowski ◽  
Diana Lu ◽  
Lindsay Julien ◽  
Lauren Rodda ◽  
Rogier A. Gaiser ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Nuclear Translocation ◽  
Strain Differences ◽  
Dense Granule ◽  
Forward Genetics ◽  
Type I ◽  
Type Ii ◽  
Granule Protein

NF-κB is an integral component of the immune response to Toxoplasma gondii. Although evidence exists that T. gondii can directly modulate the NF-κB pathway, the parasite-derived effectors involved are unknown. We determined that type II strains of T. gondii activate more NF-κB than type I or type III strains, and using forward genetics we found that this difference is a result of the polymorphic protein GRA15, a novel dense granule protein which T. gondii secretes into the host cell upon invasion. A GRA15-deficient type II strain has a severe defect in both NF-κB nuclear translocation and NF-κB–mediated transcription. Furthermore, human cells expressing type II GRA15 also activate NF-κB, demonstrating that GRA15 alone is sufficient for NF-κB activation. Along with the rhoptry protein ROP16, GRA15 is responsible for a large part of the strain differences in the induction of IL-12 secretion by infected mouse macrophages. In vivo bioluminescent imaging showed that a GRA15-deficient type II strain grows faster compared with wild-type, most likely through its reduced induction of IFN-γ. These results show for the first time that a dense granule protein can modulate host signaling pathways, and dense granule proteins can therefore join rhoptry proteins in T. gondii’s host cell–modifying arsenal.

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