GRA9, a new Toxoplasma gondii dense granule protein associated with the intravacuolar network of tubular membranes

Adjogble, Koku D.Z.; Mercier, Corinne; Dubremetz, Jean‐François; Hucke, Christian; MacKenzie, Colin R.; Cesbron-Delauw, Marie-France; Däubener, Walter

doi:10.1016/j.ijpara.2004.07.011

Cited by 47 publications

(34 citation statements)

References 28 publications

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“…The deduced amino acid sequence of GRA8 consists of a polypeptide of 267 amino acids, with an amino terminal signal peptide, 3 degenerate proline-rich repeats in the central region and a potential transmembrane domain near the carboxy terminus. GRA9 was found as a 41 kDa protein of 318 amino acids [71], which associates with the network of tubular membranes connected to the PVM. Like the other GRA proteins, GRA9 is secreted into the vacuole from the anterior end of the parasite.…”

Section: Gra8 Gra9 Gra10 Gra12 and Gra14mentioning

confidence: 99%

GRA Proteins of Toxoplasma gondii: Maintenance of Host-Parasite Interactions across the Parasitophorous Vacuolar Membrane

Nam

2009

Korean J Parasitol

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Abstract:The dense granule of Toxoplasma gondii is a secretory vesicular organelle of which the proteins participate in the modification of the parasitophorous vacuole (PV) and PV membrane for the maintenance of intracellular parasitism in almost all nucleated host cells. In this review, the archives on the research of GRA proteins are reviewed on the foci of finding GRA proteins, characterizing molecular aspects, usefulness in diagnostic antigen, and vaccine trials in addition to some functions in host-parasite interactions.

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Section: Gra8 Gra9 Gra10 Gra12 and Gra14mentioning

confidence: 99%

GRA Proteins of Toxoplasma gondii: Maintenance of Host-Parasite Interactions across the Parasitophorous Vacuolar Membrane

Nam

2009

Korean J Parasitol

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“…Most GRA proteins have been detected in close association with the membraneous system of this compartment. Hence, a fraction of the GRA1, GRA2, GRA4, GRA6, GRA7, NTPases pools, GRA8 and GRA9 has been detected more specifically associated with the vacuolar network membranes (Charif et al, 1990;Dubremetz et al, 1993;Sibley et al, 1994;Lecordier et al, 1995;Bonhomme et al, 1998;Labruyere et al, 1999;Carey et al, 2000;Adjogble et al, 2004). In these membranes, GRA2, GRA4 and GRA6 participate in the formation of a multimeric protein complex (Labruyere et al, 1999).…”

Section: Introductionmentioning

confidence: 98%

“…In the dense granule, 10 GRA proteins (GRA1 -GRA10) without sequence homology to each other (Adjogble et al, 2004;Ahn et al, 2005; reviewed by Mercier et al, 2005), 2 isoforms of nucleotide triphosphate hydrolase (NTPase I and II) (Johnson et al, 2003) and 2 protease inhibitors (TgPI 1 and 2) (Morris et al, 2002;Pszenny et al, 2002) have been previously identified in T. gondii tachyzoites. When secreted into the PV, only GRA1, TgPIs, and the NTPases remain primarily in the lumen of the vacuole (Sibley et al, Interactions between secreted GRA proteins and host cell proteins across the parasitophorous vacuolar membrane in the parasitism of Toxoplasma gondii Pszenny et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Interactions between secreted GRA proteins and host cell proteins across the parasitophorous vacuolar membrane in the parasitism of Toxoplasma gondii

Ahn

Kim

et al. 2006

Korean J Parasitol

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Abstract:Interactions between GRA proteins of dense granules in Toxoplasma gondii and host cell proteins were analyzed by yeast two-hybrid technique. The cMyc-GRA fusion proteins expressed from pGBKT7 plasmid in Y187 yeast were bound to host cell proteins from pGADT7-Rec-HeLa cDNA library transformed to AH109 yeast by mating method. By the selection procedures, a total of 939 colonies of the SD/-AHLT culture, 348 colonies of the X-α-gal positive and PCR, 157 colonies of the X-β-gal assay were chosen for sequencing the cDNA and finally 90 colonies containing ORF were selected to analyze the interactions. GRA proteins interacted with a variety of host cell proteins such as enzymes, structural and functional proteins of organellar proteins of broad spectrum. Several specific bindings of each GRA protein to host proteins were discussed presumptively the role of GRA proteins after secreting into the parasitophorous vacuoles (PV) and the PV membrane in the parasitism of this parasite.

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“…Following release from the dense granules, soluble GRA proteins are delivered to the lumen of the PV, whereas membrane-associated GRAs are trafficked to the PVM and/or the intravacuolar network (IVN), a structure that forms at the posterior end of the parasite and unfolds throughout the lumen of the vacuole (40). The IVN has been hypothesized to be involved in PV expansion and upkeep by increasing the surface area for exchange of nutrients between the parasite and its host cell (1). In addition, microscopy studies have suggested that the IVN serves as a mechanical support network for the parasite inside the PV (28).…”

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confidence: 99%

Intervacuolar Transport and Unique Topology of GRA14, a Novel Dense Granule Protein inToxoplasma gondii

et al. 2008

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Toxoplasma gondii is an obligate intracellular parasite that resides in the cytoplasm of its host in a unique membrane-bound vacuole known as the parasitophorous vacuole (PV). The membrane surrounding the parasite is remodeled by the dense granules, secretory organelles that release an array of proteins into the vacuole and to the PV membrane (PVM). Only a small portion of the protein constituents of the dense granules have been identified, and little is known regarding their roles in infection or how they are trafficked within the infected host cell. In this report, we identify a novel secreted dense granule protein, GRA14, and show that it is targeted to membranous structures within the vacuole known as the intravacuolar network and to the vacuolar membrane surrounding the parasite. We disrupted GRA14 and exploited the knockout strain to show that GRA14 can be transferred between vacuoles in a coinfection experiment with wild-type parasites. We also show that GRA14 has an unexpected topology in the PVM with its C terminus facing the host cytoplasm and its N terminus facing the vacuolar lumen. These findings have important implications both for the trafficking of GRA proteins to their ultimate destinations and for expectations of functional domains of GRA proteins at the host-parasite interface.Capable of infecting essentially any warm-blooded vertebrate, Toxoplasma gondii is one of the most successful pathogens on the planet (20, 39). Toxoplasma infects nearly onethird of the human population and causes potentially fatal disease in immunocompromised individuals and congenitally infected neonates (20). This protozoan parasite also causes ocular disease in immunocompetent individuals who are either congenitally or postnatally infected (46). As an obligate intracellular parasite, Toxoplasma enters the host cell into a nonfusogenic vacuole (the parasitophorous vacuole [PV]), in which the parasite replicates in the cytoplasm of its host. The PV membrane (PVM) is porous to small molecules (less than 1,300 Da) but otherwise serves as a boundary between the host and parasite during its intracellular survival (36).Toxoplasma invasion is mediated by a trio of specialized secretory organelles, named the micronemes, rhoptries, and dense granules, which contribute to the parasite's ability to initiate and sustain infection within its host. The first proteins secreted are from the micronemes, which release molecular adhesins that interact with the parasite's actin-myosin motor to provide the driving force for invasion (24). The rhoptries are then released and help to establish the nascent PV and modulate host cell processes (4). Lastly, proteins from the dense granules that are implicated in the remodeling and maintenance of the PV for intracellular survival are secreted (29).The precise role of dense granule proteins (GRAs) in the T. gondii life cycle is still largely unknown. To date, two groups of GRA proteins have been identified. The first group contains proteins that lack homology to organisms other than closely relat...

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GRA9, a new Toxoplasma gondii dense granule protein associated with the intravacuolar network of tubular membranes

Cited by 47 publications

References 28 publications

GRA Proteins of Toxoplasma gondii: Maintenance of Host-Parasite Interactions across the Parasitophorous Vacuolar Membrane

GRA Proteins of Toxoplasma gondii: Maintenance of Host-Parasite Interactions across the Parasitophorous Vacuolar Membrane

Interactions between secreted GRA proteins and host cell proteins across the parasitophorous vacuolar membrane in the parasitism of Toxoplasma gondii

Intervacuolar Transport and Unique Topology of GRA14, a Novel Dense Granule Protein inToxoplasma gondii

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