Biogenesis and secretion of micronemes in<i>Toxoplasma gondii</i>

Dubois, David Jean; Soldati‐Favre, Dominique

doi:10.1111/cmi.13018

Cited by 88 publications

(106 citation statements)

References 104 publications

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“…Subsequently, the rhoptries secrete a large number of proteins from the neck region that enable host cell membrane penetration and vacuole formation. 10 In addition, invasion initiates the formation of a PV, which separates the parasite from the hostile host intracellular environment. 11,12 The PV membrane (PVM) forms the physical interface between parasite and host cytoplasm, and creates a niche for parasites replication and survival.…”

Section: Introductionmentioning

confidence: 99%

Novel roles of dense granule protein 12 (GRA12) inToxoplasma gondiiinfection

et al. 2020

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are contributed equally to this work. AbstractDense granule protein 12 (GRA12) is implicated in a range of processes related to the establishment of Toxoplasma gondii infection, such as the formation of the intravacuolar network (IVN) within the parasitophorous vacuole (PV). This protein is also thought to be important for T. gondii-host interaction, pathogenesis, and immune evasion, but their exact roles remain unknown. In this study, the contributions of GRA12 to the molecular pathogenesis of T. gondii infection were examined in vitro and in vivo. Deletion of GRA12 in type I RH and type II Pru T. gondii strains did not affect the parasite growth and replication in vitro, however, it caused a significant reduction in the parasite virulence and tissue cyst burden in vivo. T. gondii Δgra12 mutants were more vulnerable to be eliminated by host immunity, without the accumulation of immunity-related GTPase a6 (Irga6) onto the PV membrane.The ultrastructure of IVN in Δgra12 mutants appeared normal, suggesting that GRA12 is not required for biogenesis of the IVN. Combined deletion of GRA12 and ROP18 induced more severe attenuation of virulence compared to single Δgra12 or Δrop18 mutant strains. These data suggest a functional association between GRA12 and ROP18 that is revealed by the severe attenuation of virulence in a double mutant relative to the single individual mutations. Future studies are needed to define the molecular basis of this putative association. Collectively these findings indicate that although GRA12 is not essential for the parasite growth and replication in vitro, it contributes to the virulence and growth of T. gondii in mice. K E Y W O R D Sdense granule protein 12, immunity-related GTPases, intravacuolar network, rhoptry protein 18, Toxoplasma gondii, virulence 3166 | WANG et Al. SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section. How to cite this article: Wang J-L, Bai M-J, Elsheikha HM, et al. Novel roles of dense granule protein 12 (GRA12) in Toxoplasma gondii infection.

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Section: Introductionmentioning

confidence: 99%

Novel roles of dense granule protein 12 (GRA12) inToxoplasma gondiiinfection

et al. 2020

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“…Both sets of secretory organelles appear to be secreted at the apex of the parasite in response to elevated intracellular Ca 2+ . Microneme exocytosis depends on a pleckstrin‐homology domain‐containing protein (APH) that is anchored by acylation to the surface of micronemes and is able to sense phosphatidic acid (PA) . Ultimately, binding of APH to PA triggers a membrane fusion event that releases the microneme content via a hypothetical SNARE‐like complex involving DOC2.1 .…”

Section: Introductionmentioning

confidence: 99%

The roles of Centrin 2 and Dynein Light Chain 8a in apical secretory organelles discharge of Toxoplasma gondii

Lentini

Dubois

Maco

et al. 2019

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To efficiently enter host cells, apicomplexan parasites such as Toxoplasma gondii rely on an apical complex composed of tubulin‐based structures as well as two sets of secretory organelles named micronemes and rhoptries. The trafficking and docking of these organelles to the apical pole of the parasite is crucial for the discharge of their contents. Here, we describe two proteins typically associated with microtubules, Centrin 2 (CEN2) and Dynein Light Chain 8a (DLC8a), that are required for efficient host cell invasion. CEN2 localizes to four different compartments, and remarkably, conditional depletion of the protein occurs in stepwise manner, sequentially depleting the protein pools from each location. This phenomenon allowed us to discern the essential function of the apical pool of CEN2 for microneme secretion, motility, invasion and egress. DLC8a localizes to the conoid, and its depletion also perturbs microneme exocytosis in addition to the apical docking of the rhoptry organelles, causing a severe defect in host cell invasion. Phenotypic characterization of CEN2 and DLC8a indicates that while both proteins participate in microneme secretion, they likely act at different steps along the cascade of events leading to organelle exocytosis.

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“…They appear as rod-like structures that are 250 nm long and 50 nm wide. They concentrate around the polar ring below the membrane system and seem to fuse with the region where only the plasma membrane exists [ 15 , 53 ]. They are the first ones to secrete their protein content, which is essential for the protozoan motion and its association with the membrane of the host cell [ 41 ].…”

Section: Biological Cycle (Transmission Pathways)mentioning

confidence: 99%

The life-cycle of Toxoplasma gondii reviewed using animations

et al. 2020

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Toxoplasma gondii is a protozoan parasite that is the causative agent of toxoplasmosis, an infection with high prevalence worldwide. Most of the infected individuals are either asymptomatic or have mild symptoms, but T. gondii can cause severe neurologic damage and even death of the fetus when acquired during pregnancy. It is also a serious condition in immunodeficient patients. The life-cycle of T. gondii is complex, with more than one infective form and several transmission pathways. In two animated videos, we describe the main aspects of this cycle, raising questions about poorly or unknown issues of T. gondii biology. Original plates, based on electron microscope observations, are also available for teachers, students and researchers. The main goal of this review is to provide a source of learning on the fundamental aspects of T. gondii biology to students and teachers contributing for better knowledge and control on this important parasite, and unique cell model. In addition, drawings and videos point to still unclear aspects of T. gondii lytic cycle that may stimulate further studies.

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Biogenesis and secretion of micronemes inToxoplasma gondii

Cited by 88 publications

References 104 publications

Novel roles of dense granule protein 12 (GRA12) inToxoplasma gondiiinfection

Novel roles of dense granule protein 12 (GRA12) inToxoplasma gondiiinfection

The roles of Centrin 2 and Dynein Light Chain 8a in apical secretory organelles discharge of Toxoplasma gondii

The life-cycle of Toxoplasma gondii reviewed using animations

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