Identification and characterization of<i>T</i><i>oxoplasma</i> SIP, a conserved apicomplexan cytoskeleton protein involved in maintaining the shape, motility and virulence of the parasite

Lentini, Gaëlle; Kong-Hap, Marie; Hajj, Hiba El; Francia, María E.; Claudet, Cyrille; Striepen, Boris; Dubremetz, Jean‐François; Lebrun, Maryse

doi:10.1111/cmi.12337

Cited by 34 publications

(37 citation statements)

References 47 publications

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“…Their localization at the transverse but not the longitudinal sutures was confirmed by co‐staining with ISC1 (Figure c). This staining pattern is similar to a previously identified protein in the transverse sutures called CBAP/SIP (Lentini et al ., ; Tilley, Krishnamurthy, Westwood, & Ward, ), which also ranked highly in the ISC4‐BioID data set (Figure e). Based on their localization, we named this new class of proteins as TSCs (CBAP/SIP was designated as TSC1).…”

Section: Resultsmentioning

confidence: 87%

“…To determine if ISC3 plays a role in parasite morphology, we examined extracellular ISC3 knockouts using light microscopy, as a similar function has been described for CBAP/SIP/TSC1 (Lentini et al ., ; Tilley et al , ). We found that disruption of ISC3 results in shorter and wider parasites, giving these knockouts a bloated appearance compared with the parental strain (Figure a).…”

Section: Resultsmentioning

confidence: 98%

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Novel insights into the composition and function of theToxoplasmaIMC sutures

Chen

Moon

Bell

et al. 2016

Cellular Microbiology

100

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Summary The Toxoplasma inner membrane complex (IMC) is a specialized organelle underlying the parasite’s plasma membrane that consists of flattened rectangular membrane sacs that are sutured together and positioned atop a supportive cytoskeleton. We have previously identified a novel class of proteins localizing to the transverse and longitudinal sutures of the IMC, which we named ISCs. Here we have used proximity-dependent biotin identification (BioID) at the sutures to better define the composition of this IMC subcompartment. Using ISC4 as bait, we demonstrate biotin-dependent labeling of the sutures and have uncovered two new ISCs. We also identified five new proteins that exclusively localize to the transverse sutures which we named TSCs, demonstrating that components of the IMC sutures consist of two groups, those that localize to the transverse and longitudinal sutures (ISCs) and those residing only in the transverse sutures (TSCs). In addition, we functionally analyze the ISC protein ISC3 and demonstrate that ISC3-null parasites have morphological defects and reduced fitness in vitro. Most importantly, Δisc3 parasites exhibit a complete loss of virulence in vivo. These studies expand the known composition of the IMC sutures and highlight the contribution of ISCs to the ability of the parasite to proliferate and cause disease.

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Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 98%

Novel insights into the composition and function of theToxoplasmaIMC sutures

Chen

Moon

Bell

et al. 2016

Cellular Microbiology

100

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“…A). Recently, it has been reported that morphological modifications affect the ability of mutant parasites to invade host cells (Lentini et al ., ). Interestingly, invasion assays allowed us to establish that the level of invasion by TgArk3‐depleted parasites was reduced to 44% of that showed by control parasites grown in the presence of ATc (Fig.…”

Section: Resultsmentioning

confidence: 97%

The conserved apicomplexan Aurora kinase TgArk3 is involved in endodyogeny, duplication rate and parasite virulence

Berry

Chen

Reininger

et al. 2016

Cellular Microbiology

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Aurora kinases are eukaryotic serine/threonine protein kinases that regulate key events associated with chromatin condensation, centrosome and spindle function, and cytokinesis. Elucidating the roles of Aurora kinases in apicomplexan parasites is crucial to understand the cell cycle control during Plasmodium schizogony or Toxoplasma endodyogeny. Here, we report on the localization of two previously uncharacterized Toxoplasma Aurora-related kinases (Ark2 and Ark3) in tachyzoites and of the uncharacterized Ark3 orthologue in Plasmodium falciparum erythrocytic stages. In T. gondii, we show that TgArk2 and TgArk3 concentrate at specific sub-cellular structures linked to parasite division: the mitotic spindle and intranuclear mitotic structures (TgArk2), and the outer core of the centrosome and the budding daughter cells cytoskeleton (TgArk3). By tagging the endogenous PfArk3 gene with the green fluorescent protein (GFP) in live parasites, we show that PfArk3 protein expression peaks late in schizogony and localizes at the periphery of budding schizonts. Disruption of the TgArk2 gene reveals no essential function for tachyzoite propagation in vitro, which is surprising giving that the P. falciparum and P. berghei orthologues are essential for erythrocyte schizogony. In contrast, knock-down of TgArk3 protein results in pronounced defects in parasite division and a major growth deficiency. TgArk3-depleted parasites display several defects, such as reduced parasite growth rate, delayed egress and parasite duplication, defect in rosette formation, reduced parasite size and invasion efficiency and lack of virulence in mice. Our study provides new insights into cell cycle control in Toxoplasma and malaria parasites, and highlights Aurora kinase 3 as potential drug target.

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“…Intracellular tachyzoites treated with low levels of the dinitroaniline oryzalin can assemble short microtubules that are sufficient to complete nuclear division and budding; these parasites have shortened subpellicular microtubules and are noninvasive, likely because they fail to adequately immobilize MyoA to power host cell entry (9). Other cytoskeletal proteins that influence shape also alter move-ment: tachyzoites lacking the IMC proteins PHIL1, SIP, and CBAP are shorter and wider than wild-type parasites and have reduced motility (128,130,131). Conoid extrusion is specifically inhibited by a small molecule, conoidin A, which was identified in a screen for invasion inhibitors (132,133).…”

Section: Microtubule-dependent Processesmentioning

confidence: 99%

Targeting Toxoplasma Tubules: Tubulin, Microtubules, and Associated Proteins in a Human Pathogen

Morrissette

2015

Eukaryot Cell

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Toxoplasma gondii is an obligate intracellular parasite that causes serious opportunistic infections, birth defects, and blindness in humans. Microtubules are critically important components of diverse structures that are used throughout the Toxoplasma life cycle. As in other eukaryotes, spindle microtubules are required for chromosome segregation during replication. Additionally, a set of membrane-associated microtubules is essential for the elongated shape of invasive "zoites," and motility follows a spiral trajectory that reflects the path of these microtubules. Toxoplasma zoites also construct an intricate, tubulin-based apical structure, termed the conoid, which is important for host cell invasion and associates with proteins typically found in the flagellar apparatus. Last, microgametes specifically construct a microtubule-containing flagellar axoneme in order to fertilize macrogametes, permitting genetic recombination. The specialized roles of these microtubule populations are mediated by distinct sets of associated proteins. This review summarizes our current understanding of the role of tubulin, microtubule populations, and associated proteins in Toxoplasma; these components are used for both novel and broadly conserved processes that are essential for parasite survival.

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Identification and characterization ofToxoplasma SIP, a conserved apicomplexan cytoskeleton protein involved in maintaining the shape, motility and virulence of the parasite

Cited by 34 publications

References 47 publications

Novel insights into the composition and function of theToxoplasmaIMC sutures

Novel insights into the composition and function of theToxoplasmaIMC sutures

The conserved apicomplexan Aurora kinase TgArk3 is involved in endodyogeny, duplication rate and parasite virulence

Targeting Toxoplasma Tubules: Tubulin, Microtubules, and Associated Proteins in a Human Pathogen

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