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Vern B Carruthers - One of the best experts on this subject based on the ideXlab platform.
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toxoplasma secretory proteins and their roles in parasite cell cycle and infection
2020Co-Authors: Maryse Lebrun, Vern B Carruthers, Mariefrance CesbrondelauwAbstract:Abstract The Apicomplexa are named for their unique apical secretory organelles: the Micronemes, the rhoptries, and the dense granules (DGs). The contents of these organelles are critical for the successful invasion and intracellular survival of Toxoplasma gondii. Microneme proteins are secreted in a calcium-dependent manner and are critical for adhesion and bridging with the host, as well as parasite egress from host cells. Rhoptry neck molecules, with Microneme proteins, form the moving junction that enables the parasite to enter the host, while other rhoptry proteins are important for modulation of host cell signaling and formation of the parasitophorous vacuole. DG proteins play important roles in the interaction with the host as well as survival within the host. This chapter provides a detailed overview of the functions of Toxoplasma secretory proteins and their roles in invasion, egress, and host cell parasitism.
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phosphatidic acid mediated signaling regulates Microneme secretion in toxoplasma
Cell Host & Microbe, 2016Co-Authors: Hayley E Bullen, Vern B Carruthers, Yonggen Jia, Yoshiki Yamaryobotte, Hugo Bisio, Ou Zhang, Natacha Klages Jemelin, Jean Baptiste Marq, Cyrille Y Botte, Dominique SoldatifavreAbstract:The obligate intracellular lifestyle of apicomplexan parasites necessitates an invasive phase underpinned by timely and spatially controlled secretion of apical organelles termed Micronemes. In Toxoplasma gondii, extracellular potassium levels and other stimuli trigger a signaling cascade culminating in phosphoinositide-phospholipase C (PLC) activation, which generates the second messengers diacylglycerol (DAG) and IP3 and ultimately results in Microneme secretion. Here we show that a delicate balance between DAG and its downstream product, phosphatidic acid (PA), is essential for controlling Microneme release. Governing this balance is the apicomplexan-specific DAG-kinase-1, which interconverts PA and DAG, and whose depletion impairs egress and causes parasite death. Additionally, we identify an acylated pleckstrin-homology (PH) domain-containing protein (APH) on the Microneme surface that senses PA during Microneme secretion and is necessary for Microneme exocytosis. As APH is conserved in Apicomplexa, these findings highlight a potentially widely used mechanism in which key lipid mediators regulate Microneme exocytosis.
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toxoplasma gondii protease tgsub1 is required for cell surface processing of micronemal adhesive complexes and efficient adhesion of tachyzoites
Cellular Microbiology, 2010Co-Authors: Vanessa Lagal, Vern B Carruthers, Emily M Binder, My Hang Huynh, Bjorn F C Kafsack, Philippa K Harris, Roberto Diez, Dawn Chen, Robert N Cole, Kami KimAbstract:Summary Host cell invasion by Toxoplasma gondii is criti- cally dependent upon adhesive proteins secreted from the Micronemes. Proteolytic trimming of Microneme contents occurs rapidly after their secretion onto the parasite surface and is pro- posed to regulate adhesive complex activation to enhance binding to host cell receptors. However, the proteases responsible and their exact function are still unknown. In this report, we show that T. gondii tachyzoites lacking the Microneme sub- tilisin protease TgSUB1 have a profound defect in surface processing of secreted Microneme proteins. Notably parasites lack protease activity responsible for proteolytic trimming of MIC2, MIC4 and M2AP after release onto the parasite surface. Although complementation with full- length TgSUB1 restores processing, complemen- tation of Dsub1 parasites with TgSUB1 lacking the GPI anchor (Dsub1::DGPISUB1) only partially restores Microneme protein processing. Loss of TgSUB1 decreases cell attachment and in vitro gliding efficiency leading to lower initial rates of invasion. Dsub1 and Dsub1::DGPISUB1 parasites are also less virulent in mice. Thus TgSUB1 is involved in micronemal protein processing and regulation of adhesive properties of macro- molecular adhesive complexes involved in host cell invasion.
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cathepsin l occupies a vacuolar compartment and is a protein maturase within the endo exocytic system of toxoplasma gondii
Molecular Microbiology, 2010Co-Authors: Fabiola Parussini, Isabelle Coppens, Parag P Shah, Scott L Diamond, Vern B CarruthersAbstract:Regulated exocytosis allows the timely delivery of proteins and other macromolecules precisely when they are needed to fulfil their functions. The intracellular parasite Toxoplasma gondii has one of the most extensive regulated exocytic systems among all unicellular organisms, yet the basis of protein trafficking and proteolytic modification in this system is poorly understood. We demonstrate that a parasite cathepsin protease, TgCPL, occupies a newly recognized vacuolar compartment (VAC) that undergoes dynamic fragmentation during T. gondii replication. We also provide evidence that within the VAC or late endosome this protease mediates the proteolytic maturation of proproteins targeted to Micronemes, regulated secretory organelles that deliver adhesive proteins to the parasite surface during cell invasion. Our findings suggest that processing of Microneme precursors occurs within intermediate endocytic compartments within the exocytic system, indicating an extensive convergence of the endocytic and exocytic pathways in this human parasite.
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a transient forward targeting element for Microneme regulated secretion in toxoplasma gondii
Biology of the Cell, 2008Co-Authors: Susannah D Brydges, Isabelle Coppens, Jill M Harper, Fabiola Parussini, Vern B CarruthersAbstract:Background information. Accurate sorting of proteins to the three types of secretory granules in Toxoplasma gondii is crucial for successful cell invasion by this obligate intracellular parasite. As in other eukaryotic systems, propeptide sequences are a common yet poorly understood feature of proteins destined for regulated secretion, which for Toxoplasma occurs through two distinct invasion organelles, rhoptries and Micronemes. Microneme discharge during parasite apical attachment plays a pivotal role in cell invasion by delivering adhesive proteins for host receptor engagement. Results. We show here that the small micronemal proprotein MIC5 (Microneme protein-5) undergoes proteolytic maturation at a site beyond the Golgi, and only the processed form of MIC5 is secreted via the Micronemes. Proper cleavage of the MIC5 propeptide relies on an arginine residue in the P1′ position, although P1′ mutants are still cleaved to a lesser extent at an alternative site downstream of the primary site. Nonetheless, this aberrantly cleaved species still correctly traffics to the Micronemes, indicating that correct cleavage is not necessary for micronemal targeting. In contrast, a deletion mutant lacking the propeptide was retained within the secretory system, principally in the ER (endoplasmic reticulum). The MIC5 propeptide also supported correct trafficking when exchanged for the M2AP propeptide, which was recently shown to also be required for micronemal trafficking of the TgMIC2 (T. gondii MIC2)–M2AP complex [Harper, Huynh, Coppens, Parussini, Moreno and Carruthers (2006) Mol. Biol. Cell 17, 4551–4563]. Conclusion. Our results illuminate common and unique features of micronemal propeptides in their role as trafficking facilitators.
Frank Lafont - One of the best experts on this subject based on the ideXlab platform.
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Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication
PLoS Pathogens, 2020Co-Authors: Kannan Venugopal, Elisabeth Werkmeister, Gordon Langsley, Frank Lafont, Nicolas Barois, Sylia Chehade, Javier Periz, Isabelle Tardieux, Jamal Khalife, Markus MeissnerAbstract:Toxoplasma gondii possesses an armada of secreted virulent factors that enable parasite invasion and survival into host cells. These factors are contained in specific secretory organelles, the rhoptries, Micronemes and dense granules that release their content upon host cell recognition. Dense granules are secreted in a constitutive manner during parasite replication and play a crucial role in modulating host metabolic and immune responses. While the molecular mechanisms triggering rhoptry and Microneme release upon host cell adhesion have been well studied, constitutive secretion remains a poorly explored aspect of T. gondii vesicular trafficking. Here, we investigated the role of the small GTPase Rab11A, a known regulator of exocytosis in eukaryotic cells. Our data revealed an essential role of Rab11A in promoting the cytoskeleton driven transport of dense granules and the release of their content into the vacuolar space. Rab11A also regulates transmembrane protein trafficking and localization during parasite replication, indicating a broader role of Rab11A in cargo exocytosis at the plasma membrane. Moreover, we found that Rab11A also regulates extracellular parasite motility and adhesion to host cells. In line with these findings, MIC2 secretion was altered in Rab11A-defective parasites, which also exhibited severe morphological defects. Strikingly, by live imaging we observed a polarized accumulation of Rab11A-positive vesicles and dense granules at the apical pole of extracellular motile and invading parasites suggesting that apically polarized Rab11A-dependent delivery of cargo regulates early secretory events during parasite entry into host cells.
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Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry and Microneme proteins and in parasite division.
PLoS pathogens, 2017Co-Authors: Elisabeth Werkmeister, Fabien Sindikubwabo, Mohamed-ali Hakimi, Gordon Langsley, Frank Lafont, Kannan Venugopal, Nicolas Barois, Jean-michel Saliou, Anaïs F. Poncet, Ludovic HuotAbstract:Toxoplasma gondii possesses a highly polarized secretory system, which efficiently assembles de novo Micronemes and rhoptries during parasite replication. These apical secretory organelles release their contents into host cells promoting parasite invasion and survival. Using a CreLox-based inducible knock-out strategy and the ddFKBP over-expression system, we unraveled novel functions of the clathrin adaptor complex TgAP1. First, our data indicate that AP1 in T. gondii likely functions as a conserved heterotetrameric complex composed of the four subunits γ, β, μ1, σ1 and interacts with known regulators of clathrin-mediated vesicular budding such as the unique ENTH-domain containing protein, which we named Epsin-like protein (TgEpsL). Disruption of the μ1 subunit resulted in the mis-sorting of Microneme proteins at the level of the Trans-Golgi-Network (TGN). Furthermore, we demonstrated that TgAP1 regulates rhoptry biogenesis by activating rhoptry protein exit from the TGN, but also participates in the post-Golgi maturation process of preROP compartments into apically anchored club-shaped mature organelles. For this latter activity, our data indicate a specific functional relationship between TgAP1 and the Rab5A-positive endosome-like compartment. In addition, we unraveled an original role for TgAP1 in the regulation of parasite division. APμ1-depleted parasites undergo normal daughter cell budding and basal complex assembly but fail to segregate at the end of cytokinesis.
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Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry and Microneme proteins and in parasite division - Table 4
2017Co-Authors: Kannan Venugopal, Elisabeth Werkmeister, Fabien Sindikubwabo, Mohamed-ali Hakimi, Gordon Langsley, Nicolas Barois, Jean-michel Saliou, Ludovic Huot, Anais Poncet, Frank LafontAbstract:Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry and Microneme proteins and in parasite division - Table
David L Sibley - One of the best experts on this subject based on the ideXlab platform.
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high throughput measurement of Microneme secretion in toxoplasma gondii
Methods of Molecular Biology, 2020Co-Authors: David L Sibley, Kevin M Brown, Sebastian LouridoAbstract:Micronemes are specialized secretory organelles present in all motile forms of apicomplexan parasites. Microneme vesicles hold adhesins and other proteins that are secreted to facilitate parasite attachment, invasion of host cells, and egress following replication-all processes indispensable for cell-to-cell transmission of these obligate intracellular parasites. Defining the signaling pathways that lead to Microneme secretion is an important part of understanding the infectious cycle of apicomplexan parasites. However, the classical method of measuring Microneme secretion by immunoblotting for Microneme proteins in parasite excreted/secreted antigen (ESA) preparations is low-throughput and only semiquantitative. We recently reported a new luciferase-based method for measuring Microneme secretion in a 96-well format with high sensitivity in the model apicomplexan Toxoplasma gondii. Here, we aim to elaborate on this detection method and review current practices for stimulating Microneme secretion in vitro.
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serum albumin stimulates protein kinase g dependent Microneme secretion in toxoplasma gondii
Journal of Biological Chemistry, 2016Co-Authors: Kevin M Brown, Sebastian Lourido, David L SibleyAbstract:Microneme secretion is essential for motility, invasion, and egress in apicomplexan parasites. Although previous studies indicate that Ca(2+) and cGMP control Microneme secretion, little is known about how these pathways are naturally activated. Here we have developed genetically encoded indicators for Ca(2+) and Microneme secretion to better define the signaling pathways that regulate these processes in Toxoplasma gondii We found that Microneme secretion was triggered in vitro by exposure to a single host protein, serum albumin. The natural agonist serum albumin induced Microneme secretion in a protein kinase G-dependent manner that correlated with increased cGMP levels. Surprisingly, serum albumin acted independently of elevated Ca(2+) and yet it was augmented by artificial agonists that raise Ca(2+), such as ethanol. Furthermore, although ethanol elevated intracellular Ca(2+), it alone was unable to trigger secretion without the presence of serum or serum albumin. This dichotomy was recapitulated by zaprinast, a phosphodiesterase inhibitor that elevated cGMP and separately increased Ca(2+) in a protein kinase G-independent manner leading to Microneme secretion. Taken together, these findings reveal that Microneme secretion is centrally controlled by protein kinase G and that this pathway is further augmented by elevation of intracellular Ca(2.)
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calcium dependent protein kinase 1 is an essential regulator of exocytosis in toxoplasma
Nature, 2010Co-Authors: Sebastian Lourido, Joel L Shuman, Chao Zhang, Kevan M Shokat, R Hui, David L SibleyAbstract:Calcium-regulated exocytosis is a ubiquitous process in eukaryotes, whereby secretory vesicles fuse with the plasma membrane and release their contents in response to an intracellular calcium surge. This process regulates various cellular functions such as plasma membrane repair in plants and animals, the discharge of defensive spikes in Paramecium, and the secretion of insulin from pancreatic cells, immune modulators from lymphocytes, and chemical transmitters from neurons. In animal cells, serine/threonine kinases including cAMP-dependent protein kinase, protein kinase C and calmodulin kinases have been implicated in calcium-signal transduction leading to regulated secretion. Although plants and protozoa also regulate secretion by means of intracellular calcium, the method by which these signals are relayed has not been explained. Here we show that the Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) is an essential regulator of calcium-dependent exocytosis in this opportunistic human pathogen. Conditional suppression of TgCDPK1 revealed that it controls calcium-dependent secretion of specialized organelles called Micronemes, resulting in a block of essential phenotypes including parasite motility, host-cell invasion, and egress. These phenotypes were recapitulated by using a chemical biology approach in which pyrazolopyrimidine-derived compounds specifically inhibited TgCDPK1 and disrupted the parasite's life cycle at stages dependent on Microneme secretion. Inhibition was specific to TgCDPK1, because expression of a resistant mutant kinase reversed sensitivity to the inhibitor. TgCDPK1 is conserved among apicomplexans and belongs to a family of kinases shared with plants and ciliates, suggesting that related CDPKs may have a function in calcium-regulated secretion in other organisms. Because this kinase family is absent from mammalian hosts, it represents a validated target that may be exploitable for chemotherapy against T. gondii and related apicomplexans.
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Microneme rhomboid protease tgrom1 is required for efficient intracellular growth of toxoplasma gondii
Eukaryotic Cell, 2008Co-Authors: Fabien Brossier, Lucas G Starnes, Wandy L. Beatty, David L SibleyAbstract:Rhomboids are serine proteases that cleave their substrates within the transmembrane domain. Toxoplasma gondii contains six rhomboids that are expressed in different life cycle stages and localized to different cellular compartments. Toxoplasma rhomboid protein 1 (TgROM1) has previously been shown to be active in vitro, and the orthologue in Plasmodium falciparum processes the essential Microneme protein AMA1 in a heterologous system. We investigated the role of TgROM1 to determine its role during in vitro growth of T. gondii. TgROM1 was localized in the secretory pathway of the parasite, including the Golgi apparatus and Micronemes, which contain adhesive proteins involved in invasion of host cells. However, unlike other micronemal proteins, TgROM1 was not released onto the parasite surface during cell invasion, suggesting it does not play a critical role in cell invasion. Suppression of TgROM1 using the tetracycline-regulatable system revealed that ROM1-deficient parasites were outcompeted by wild-type T. gondii. ROM1-deficient parasites showed only modest decrease in invasion but replicated more slowly than wild-type cells. Collectively, these results indicate that ROM1 is required for efficient intracellular growth by T. gondii.
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toxoplasma gondii Microneme protein mic2
The International Journal of Biochemistry & Cell Biology, 2005Co-Authors: Fabien Brossier, David L SibleyAbstract:The phylum Apicomplexa contains parasites responsible for a variety of diseases including malaria, cryptosporidiosis, and toxoplasmosis. One of the common features of these parasites is that they contain a set of apical organelles whose sequential secretion is required for the invasion of host cells. Microneme proteins are the main adhesins involved in the attachment to the host cell surface by apicomplexans. The Microneme protein MIC2, produced by Toxoplasma gondii, is conserved in apicomplexans and serves as a model to understand the first steps of invasion by the phylum. New data about the structure-function relationship of MIC2 reinforce the critical role of this protein in the successful invasion of cells by Toxoplasma and reveal potential therapeutic targets that may be used to control toxoplasmosis.
Kannan Venugopal - One of the best experts on this subject based on the ideXlab platform.
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Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication
PLoS Pathogens, 2020Co-Authors: Kannan Venugopal, Elisabeth Werkmeister, Gordon Langsley, Frank Lafont, Nicolas Barois, Sylia Chehade, Javier Periz, Isabelle Tardieux, Jamal Khalife, Markus MeissnerAbstract:Toxoplasma gondii possesses an armada of secreted virulent factors that enable parasite invasion and survival into host cells. These factors are contained in specific secretory organelles, the rhoptries, Micronemes and dense granules that release their content upon host cell recognition. Dense granules are secreted in a constitutive manner during parasite replication and play a crucial role in modulating host metabolic and immune responses. While the molecular mechanisms triggering rhoptry and Microneme release upon host cell adhesion have been well studied, constitutive secretion remains a poorly explored aspect of T. gondii vesicular trafficking. Here, we investigated the role of the small GTPase Rab11A, a known regulator of exocytosis in eukaryotic cells. Our data revealed an essential role of Rab11A in promoting the cytoskeleton driven transport of dense granules and the release of their content into the vacuolar space. Rab11A also regulates transmembrane protein trafficking and localization during parasite replication, indicating a broader role of Rab11A in cargo exocytosis at the plasma membrane. Moreover, we found that Rab11A also regulates extracellular parasite motility and adhesion to host cells. In line with these findings, MIC2 secretion was altered in Rab11A-defective parasites, which also exhibited severe morphological defects. Strikingly, by live imaging we observed a polarized accumulation of Rab11A-positive vesicles and dense granules at the apical pole of extracellular motile and invading parasites suggesting that apically polarized Rab11A-dependent delivery of cargo regulates early secretory events during parasite entry into host cells.
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Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry and Microneme proteins and in parasite division.
PLoS pathogens, 2017Co-Authors: Elisabeth Werkmeister, Fabien Sindikubwabo, Mohamed-ali Hakimi, Gordon Langsley, Frank Lafont, Kannan Venugopal, Nicolas Barois, Jean-michel Saliou, Anaïs F. Poncet, Ludovic HuotAbstract:Toxoplasma gondii possesses a highly polarized secretory system, which efficiently assembles de novo Micronemes and rhoptries during parasite replication. These apical secretory organelles release their contents into host cells promoting parasite invasion and survival. Using a CreLox-based inducible knock-out strategy and the ddFKBP over-expression system, we unraveled novel functions of the clathrin adaptor complex TgAP1. First, our data indicate that AP1 in T. gondii likely functions as a conserved heterotetrameric complex composed of the four subunits γ, β, μ1, σ1 and interacts with known regulators of clathrin-mediated vesicular budding such as the unique ENTH-domain containing protein, which we named Epsin-like protein (TgEpsL). Disruption of the μ1 subunit resulted in the mis-sorting of Microneme proteins at the level of the Trans-Golgi-Network (TGN). Furthermore, we demonstrated that TgAP1 regulates rhoptry biogenesis by activating rhoptry protein exit from the TGN, but also participates in the post-Golgi maturation process of preROP compartments into apically anchored club-shaped mature organelles. For this latter activity, our data indicate a specific functional relationship between TgAP1 and the Rab5A-positive endosome-like compartment. In addition, we unraveled an original role for TgAP1 in the regulation of parasite division. APμ1-depleted parasites undergo normal daughter cell budding and basal complex assembly but fail to segregate at the end of cytokinesis.
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Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry and Microneme proteins and in parasite division - Table 4
2017Co-Authors: Kannan Venugopal, Elisabeth Werkmeister, Fabien Sindikubwabo, Mohamed-ali Hakimi, Gordon Langsley, Nicolas Barois, Jean-michel Saliou, Ludovic Huot, Anais Poncet, Frank LafontAbstract:Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry and Microneme proteins and in parasite division - Table
Elisabeth Werkmeister - One of the best experts on this subject based on the ideXlab platform.
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Rab11A regulates dense granule transport and secretion during Toxoplasma gondii invasion of host cells and parasite replication
PLoS Pathogens, 2020Co-Authors: Kannan Venugopal, Elisabeth Werkmeister, Gordon Langsley, Frank Lafont, Nicolas Barois, Sylia Chehade, Javier Periz, Isabelle Tardieux, Jamal Khalife, Markus MeissnerAbstract:Toxoplasma gondii possesses an armada of secreted virulent factors that enable parasite invasion and survival into host cells. These factors are contained in specific secretory organelles, the rhoptries, Micronemes and dense granules that release their content upon host cell recognition. Dense granules are secreted in a constitutive manner during parasite replication and play a crucial role in modulating host metabolic and immune responses. While the molecular mechanisms triggering rhoptry and Microneme release upon host cell adhesion have been well studied, constitutive secretion remains a poorly explored aspect of T. gondii vesicular trafficking. Here, we investigated the role of the small GTPase Rab11A, a known regulator of exocytosis in eukaryotic cells. Our data revealed an essential role of Rab11A in promoting the cytoskeleton driven transport of dense granules and the release of their content into the vacuolar space. Rab11A also regulates transmembrane protein trafficking and localization during parasite replication, indicating a broader role of Rab11A in cargo exocytosis at the plasma membrane. Moreover, we found that Rab11A also regulates extracellular parasite motility and adhesion to host cells. In line with these findings, MIC2 secretion was altered in Rab11A-defective parasites, which also exhibited severe morphological defects. Strikingly, by live imaging we observed a polarized accumulation of Rab11A-positive vesicles and dense granules at the apical pole of extracellular motile and invading parasites suggesting that apically polarized Rab11A-dependent delivery of cargo regulates early secretory events during parasite entry into host cells.
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Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry and Microneme proteins and in parasite division.
PLoS pathogens, 2017Co-Authors: Elisabeth Werkmeister, Fabien Sindikubwabo, Mohamed-ali Hakimi, Gordon Langsley, Frank Lafont, Kannan Venugopal, Nicolas Barois, Jean-michel Saliou, Anaïs F. Poncet, Ludovic HuotAbstract:Toxoplasma gondii possesses a highly polarized secretory system, which efficiently assembles de novo Micronemes and rhoptries during parasite replication. These apical secretory organelles release their contents into host cells promoting parasite invasion and survival. Using a CreLox-based inducible knock-out strategy and the ddFKBP over-expression system, we unraveled novel functions of the clathrin adaptor complex TgAP1. First, our data indicate that AP1 in T. gondii likely functions as a conserved heterotetrameric complex composed of the four subunits γ, β, μ1, σ1 and interacts with known regulators of clathrin-mediated vesicular budding such as the unique ENTH-domain containing protein, which we named Epsin-like protein (TgEpsL). Disruption of the μ1 subunit resulted in the mis-sorting of Microneme proteins at the level of the Trans-Golgi-Network (TGN). Furthermore, we demonstrated that TgAP1 regulates rhoptry biogenesis by activating rhoptry protein exit from the TGN, but also participates in the post-Golgi maturation process of preROP compartments into apically anchored club-shaped mature organelles. For this latter activity, our data indicate a specific functional relationship between TgAP1 and the Rab5A-positive endosome-like compartment. In addition, we unraveled an original role for TgAP1 in the regulation of parasite division. APμ1-depleted parasites undergo normal daughter cell budding and basal complex assembly but fail to segregate at the end of cytokinesis.
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Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry and Microneme proteins and in parasite division - Table 4
2017Co-Authors: Kannan Venugopal, Elisabeth Werkmeister, Fabien Sindikubwabo, Mohamed-ali Hakimi, Gordon Langsley, Nicolas Barois, Jean-michel Saliou, Ludovic Huot, Anais Poncet, Frank LafontAbstract:Dual role of the Toxoplasma gondii clathrin adaptor AP1 in the sorting of rhoptry and Microneme proteins and in parasite division - Table
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Toxoplasma Sortilin-like Receptor Regulates Protein Transport and Is Essential for Apical Secretory Organelle Biogenesis and Host Infection
Cell Host and Microbe, 2012Co-Authors: Pierre-julien Sloves, Elisabeth Werkmeister, Stephane Delhaye, Thomas Mouveaux, Christian Slomianny, Agnes Hovasse, Tchilabalo Dilezitoko Alayi, Isabelle Callebaut, Rajshekhar Y. Gaji, Christine Schaeffer-reissAbstract:Apicomplexan parasites have an assortment of unique apical secretory organelles (rhoptries and Micronemes), which have crucial functions in host infection. Here, we show that a Toxoplasma gondii sortilin-like receptor (TgSORTLR) is required for the subcellular localization and formation of apical secretory organelles.TgSORTLR is a transmembrane protein that resides within Golgi-endosomal related compartments. The lumenal domain specifically interacts with rhoptry and Microneme proteins, while the cytoplasmic tail of TgSORTLR recruits cytosolic sorting machinery involved in anterograde and retrograde protein transport. Ectopic expression of the N-terminal TgSORTLR lumenal domain results in dominant negative effects with the mislocalization of both endogenous TgSORTLR as well as rhoptry and Microneme proteins. Conditional ablation of TgSORTLR disrupts rhoptry and Microneme biogenesis, inhibits parasite motility, and blocks both invasion into and egress from host cells. Thus, the sortilin-like receptor is essential for protein trafficking and the biogenesis of key secretory organelles in Toxoplasma.