TgGRA23, a novel Toxoplasma gondii dense granule protein associated with the parasitophorous vacuole membrane and intravacuolar network

Masatani, Tatsunori; Matsuo, Tomohide; Tanaka, Tetsuya; Terkawi, Mohamad Alaa; Lee, Eung-goo; Goo, Youn‐Kyoung; Aboge, Gabriel Oluga; Yamagishi, Junya; Hayashi, Kei; Kameyama, Kyohko; Cao, Shinuo; Nishikawa, Yoshifumi; Xuan, Xuenan

doi:10.1016/j.parint.2013.04.003

Cited by 17 publications

(11 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, the majority of GRA17 is tightly associated with the PVM. A similar fractionation pattern for GRA23 has been reported (Masatani et al, 2013). …”

Section: Resultssupporting

confidence: 86%

“…1A). GRA23 has previously been characterized as a PVM-localized GRA (Masatani et al, 2013) and to observe its relative co-localization with GRA17 we generated a strain that co-expresses GRA17-V5 and GRA23-HF (the tachyzoites express GFP) and observed substantial co-localization around the PVM (Fig. 1A, bottom panel ; Fig.…”

Section: Resultsmentioning

confidence: 98%

“…Since EXP2 has been implicated in forming a molecular-translocation channel in the P. falciparum PVM, we searched for homologs in the Toxoplasma genome, and found two genes encoding proteins with predicted signal peptides: the uncharacterized TGGT1_222170 and TgGRA23 ( TGGT1_297880 ), an identified GRA gene of unknown function (Masatani et al, 2013). TGGT1_222170 and Tg GRA23 share 30% amino acid sequence similarity with each other and 26% and 22% similarity with Pf EXP2, respectively (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of Small Molecules between the Host and the Parasitophorous Vacuole

Gold

Kaplan

Lis

et al. 2015

Cell Host & Microbe

212

249

View full text Add to dashboard Cite

Summary Toxoplasma gondii is a protozoan pathogen in the phylum Apicomplexa that resides within an intracellular parasitophorous vacuole (PV) that is selectively permeable to small molecules through unidentified mechanisms. We have identified GRA17 as a Toxoplasma-secreted protein that localizes to the parasitophorous vacuole membrane (PVM) and mediates passive transport of small molecules across the PVM. GRA17 is related to the putative Plasmodium translocon protein EXP2 and conserved across PV-residing Apicomplexa. The PVs of GRA17-deficient parasites have aberrant morphology, reduced permeability to small molecules, and structural instability. GRA17-deficient parasites proliferate slowly and are avirulent in mice. These GRA17-deficient phenotypes are rescued by complementation with Plasmodium EXP2. GRA17 functions synergistically with a related protein, GRA23. Exogenous expression of GRA17 or GRA23 alters the membrane conductance properties of Xenopus oocytes in a manner consistent with a large non-selective pore. Thus, GRA17 and GRA23 provide a molecular basis for PVM permeability and nutrient access.

show abstract

“…Thus, the majority of GRA17 is tightly associated with the PVM. A similar fractionation pattern for GRA23 has been reported (Masatani et al, 2013). …”

Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of Small Molecules between the Host and the Parasitophorous Vacuole

Gold

Kaplan

Lis

et al. 2015

Cell Host & Microbe

212

249

View full text Add to dashboard Cite

show abstract

“…This observation supports the idea of an association of MAG1 with these filamentous structures since the diffusion rate of MAG1-mScarlet is limited in the bradyzoite stage but not in the tachyzoite stage. MAG1 and MAG2 may associate with the intracyst network in a manner similar to how various GRAs associate with the intravacuolar network of the tachyzoite stage (48)(49)(50). The results of the fractionation experiment show that both MAG2 and MAG1 have soluble and insoluble forms (Fig.…”

Section: Discussionmentioning

confidence: 77%

MAG2, a Toxoplasma gondii Bradyzoite Stage-Specific Cyst Matrix Protein

Mayoral

Yakubu

et al. 2020

mSphere

View full text Add to dashboard Cite

Toxoplasma gondii causes a chronic infection that affects a significant portion of the world's population, and this latent infection is the source of reactivation of toxoplasmosis. An attribute of the slowly growing bradyzoite stage of the parasite is the formation of a cyst within infected cells, allowing the parasite to escape the host's immune response. In this study, a new bradyzoite cyst matrix antigen (MAG) was identified through a hybridoma library screen. This cyst matrix antigen, matrix antigen 2 (MAG2), contains 14 tandem repeats consisting of acidic, basic, and proline residues. Immunoblotting revealed that MAG2 migrates at a level higher than its predicted molecular weight, and computational analysis showed that the structure of MAG2 is highly disordered. Cell fractionation studies indicated that MAG2 was associated with both insoluble and soluble cyst matrix material, suggesting that it interacts with the intracyst network (ICN). Examination of the kinetics of MAG2 within the cyst matrix using fluorescence recovery after photobleaching (FRAP) demonstrated that MAG2 does not readily diffuse within the cyst matrix. Kinetic studies of MAG1 demonstrated that this protein has different diffusion kinetics in tachyzoite and bradyzoite vacuoles and that its mobility is not altered in the absence of MAG2. In addition, deletion of MAG2 does not influence growth, cystogenesis, or cyst morphology. IMPORTANCE This report expands on the list of characterized Toxoplasma gondii cyst matrix proteins. Using fluorescence recovery after photobleaching (FRAP), we have shown that matrix proteins within the cyst matrix are not mainly in a mobile state, providing further evidence of how proteins behave within the cyst matrix. Understanding the proteins expressed during the bradyzoite stage of the parasite reveals how the parasite functions during chronic infection. KEYWORDS latency, monoclonal antibody screen, intravacuolar network, MAG1, MAG2, Toxoplasma gondii, bradyzoite, cyst matrix, fluorescence recovery after photobleaching (FRAP) E xposure to contaminated food containing bradyzoites, which represent the latent stage of Toxoplasma gondii, or to oocysts containing sporozoites, which represent the sexual stage of the parasite, results in the transmission of this parasite (1). In the case of pregnant mothers, first-time exposure may lead to complications within the unborn fetus (2). While the levels of seroprevalence of T. gondii differ from country to country (3), it is estimated that 30% to 40% of the human population is latently infected with this parasite. There is currently no cure for this infection in the latent stage, and it is believed that this organism can persist for life in its hosts. The persistence of the infection is due to the ability of the parasite to differentiate from tachyzoites, representing the quickly proliferating stage, into bradyzoites, which can remain dormant within cysts for many years. When the host's immune system is weakened, the parasite FIG 2 20C3 MAb recognizes MAG2, a disordered 218-...

show abstract

“…Infection during pregnancy can result in feeble offspring, abortion and stillbirth, or birth defects. Moreover, ocular diseases have been reported as toxoplasmosis outcome, that can sometimes be severe in adults resulting in loss of vision and cognitive function and even fatal encephalitis [8,9]. There are three infectious stages of T. gondii sporozoites (in oocysts), slow growing bradyzoites (in tissue cysts) and rapidly dividing tachyzoites (in pseudocysts) which can be transmitted through two main routes (sexual and asexual) [8].…”

Section: Introductionmentioning

confidence: 99%

Detection of Toxoplasma gondii from Native Cattle in Southwest of Iran

Arshi¹

2015

AVS

View full text Add to dashboard Cite

Infections by protozoan parasite Toxoplasma gondii are prevalent worldwide in animals and human. T. gondii is the causative agent of toxoplasmosis, one of the most prevalent parasitic infections to humans and domestic animals. If first be during pregnancy, T. gondii may be transferred vertically by tachyzoites that are passed to the embryo via the placenta. T. gondii may be transmitted horizontally in three phases of the life cycle, ingesting infectious oocysts from the environment or tissue cysts or tachyzoites which are contained in gastrointestinal of many different animals. Transmission may also occur via tachyzoites contained in blood products, texture transplants or non-pasteurized milk. Like rest of the world toxoplasmosis is prevalent in Iran. The present study aimed to determine T. gondii isolates from native cattle in Chaharmahal Va Bakhtiari province located in south west of Iran by molecular methods. In this study, 155 blood samples were collected from native cattle. Genomic DNA was extracted using DNA extraction Kit (Cinna Gen, Iran) according to the manufacturer protocol and PCR was performed using specific primers (ITS-F and ITS-R). Sixteen (6.95%) cattle were positive to T. gondii infection. The positive control samples showed the excepted amplification product specific for T. gondii (171 bp). Although the present results showed relatively low prevalence of T.gondii infection in Chaharmahal Va Bakhtiari native cattle, control and eradication programs seem to be still necessary to prevent the prevalence of this infection factor and economic losses.

show abstract

TgGRA23, a novel Toxoplasma gondii dense granule protein associated with the parasitophorous vacuole membrane and intravacuolar network

Cited by 17 publications

References 29 publications

The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of Small Molecules between the Host and the Parasitophorous Vacuole

The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of Small Molecules between the Host and the Parasitophorous Vacuole

MAG2, a Toxoplasma gondii Bradyzoite Stage-Specific Cyst Matrix Protein

Detection of Toxoplasma gondii from Native Cattle in Southwest of Iran

Contact Info

Product

Resources

About