Fundamental Roles of the Golgi-Associated Toxoplasma Aspartyl Protease, ASP5, at the Host-Parasite Interface
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{"title"=>"Fundamental Roles of the Golgi-Associated Toxoplasma Aspartyl Protease, ASP5, at the Host-Parasite Interface", "type"=>"journal", "authors"=>[{"first_name"=>"Pierre Mehdi", "last_name"=>"Hammoudi", "scopus_author_id"=>"56062888800"}, {"first_name"=>"Damien", "last_name"=>"Jacot", "scopus_author_id"=>"55342182600"}, {"first_name"=>"Christina", "last_name"=>"Mueller", "scopus_author_id"=>"7202002300"}, {"first_name"=>"Manlio", "last_name"=>"Di Cristina", "scopus_author_id"=>"6602478847"}, {"first_name"=>"Sunil Kumar", "last_name"=>"Dogga", "scopus_author_id"=>"56940768700"}, {"first_name"=>"Jean Baptiste", "last_name"=>"Marq", "scopus_author_id"=>"6507986627"}, {"first_name"=>"Julia", "last_name"=>"Romano", "scopus_author_id"=>"7103391512"}, {"first_name"=>"Nicolò", "last_name"=>"Tosetti", "scopus_author_id"=>"56320255300"}, {"first_name"=>"Juan", "last_name"=>"Dubrot", "scopus_author_id"=>"23008258800"}, {"first_name"=>"Yalin", "last_name"=>"Emre", "scopus_author_id"=>"9236856800"}, {"first_name"=>"Matteo", "last_name"=>"Lunghi", "scopus_author_id"=>"56587680400"}, {"first_name"=>"Isabelle", "last_name"=>"Coppens", "scopus_author_id"=>"6604095394"}, {"first_name"=>"Masahiro", "last_name"=>"Yamamoto", "scopus_author_id"=>"55552856200"}, {"first_name"=>"Daniel", "last_name"=>"Sojka", "scopus_author_id"=>"15081887100"}, {"first_name"=>"Paco", "last_name"=>"Pino", "scopus_author_id"=>"7007124664"}, {"first_name"=>"Dominique", "last_name"=>"Soldati-Favre", "scopus_author_id"=>"8235046700"}], "year"=>2015, "source"=>"PLoS Pathogens", "identifiers"=>{"scopus"=>"2-s2.0-84946057470", "sgr"=>"84946057470", "issn"=>"15537374", "doi"=>"10.1371/journal.ppat.1005211", "pmid"=>"26473595", "isbn"=>"1553-7374 (Electronic)\r1553-7366 (Linking)", "pui"=>"606741129"}, "id"=>"705c8fdb-71b8-3c6e-a87f-d923e983b90c", "abstract"=>"Toxoplasma gondii possesses sets of dense granule proteins (GRAs) that either assemble at, or cross the parasitophorous vacuole membrane (PVM) and exhibit motifs resembling the HT/PEXEL previously identified in a repertoire of exported Plasmodium proteins. Within Plasmodium spp., cleavage of the HT/PEXEL motif by the endoplasmic reticulum-resident protease Plasmepsin V precedes trafficking to and export across the PVM of proteins involved in pathogenicity and host cell remodelling. Here, we have functionally characterized the T. gondii aspartyl protease 5 (ASP5), a Golgi-resident protease that is phylogenetically related to Plasmepsin V. We show that deletion of ASP5 causes a significant loss in parasite fitness in vitro and an altered virulence in vivo. Furthermore, we reveal that ASP5 is necessary for the cleavage of GRA16, GRA19 and GRA20 at the PEXEL-like motif. In the absence of ASP5, the intravacuolar nanotubular network disappears and several GRAs fail to localize to the PVM, while GRA16 and GRA24, both known to be targeted to the host cell nucleus, are retained within the vacuolar space. Additionally, hypermigration of dendritic cells and bradyzoite cyst wall formation are impaired, critically impacting on parasite dissemination and persistence. Overall, the absence of ASP5 dramatically compromises the parasite's ability to modulate host signalling pathways and immune responses.", "link"=>"http://www.mendeley.com/research/fundamental-roles-golgiassociated-toxoplasma-aspartyl-protease-asp5-hostparasite-interface", "reader_count"=>42, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>8, "Student > Bachelor"=>5, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>8, "Student > Bachelor"=>5, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>24, "Medicine and Dentistry"=>2, "Neuroscience"=>1, "Chemistry"=>2, "Computer Science"=>2, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>24}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>2, "Israel"=>1, "Germany"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2362714"], "description"=>"<p>(A) Induced bradyzoite differentiation of type II parasites under high pH conditions. In parasites lacking ASP5, cyst wall formation, as visualized with DBA lectin, was already affected 1 week after induced-differentiation. α-SAG4 (surface antigen 4) and α-BAG1 (bradyzoite antigen 1) were used as bradyzoite markers. GFP is under the control of a bradyzoite lactate dehydrogenase 2 (LDH2) promoter. Scale bars represent 2 μm. (B) Quantification of the representative IFAs depicted in panel (A). Data are mean value ± s.d. of three independent experiments.</p>", "links"=>[], "tags"=>["host cell remodelling", "host cell nucleus", "parasite", "ht", "bradyzoite cyst wall formation", "intravacuolar nanotubular network", "gra", "ASP 5 causes", "pvm", "gondii aspartyl protease 5", "motif", "parasitophorous vacuole membrane", "protein", "ASP 5"], "article_id"=>1577851, "categories"=>["Biological Sciences"], "users"=>["Pierre-Mehdi Hammoudi", "Damien Jacot", "Christina Mueller", "Manlio Di Cristina", "Sunil Kumar Dogga", "Jean-Baptiste Marq", "Julia Romano", "Nicolò Tosetti", "Juan Dubrot", "Yalin Emre", "Matteo Lunghi", "Isabelle Coppens", "Masahiro Yamamoto", "Daniel Sojka", "Paco Pino", "Dominique Soldati-Favre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005211.g008", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cyst_wall_formation_is_affected_in_type_II_parasites_lacking_ASP5_/1577851", "title"=>"Cyst wall formation is affected in type II parasites lacking ASP5.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 02:58:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2362699"], "description"=>"<p>(A) In the absence of ASP5, GRA16-3Myc transiently transfected in type I parasites was no longer addressed to the host nucleus (white arrowheads) and instead remained within the PV. Scale bars represent 2 μm. (B) The PEXEL-like motif-containing GRA16-3Myc displays an altered cleavage profile in <i>RHΔasp5</i> and <i>RHΔasp5</i>/<i>asp5c-D/A</i> parasites as detected by western blot analyses. R1 and R2: repeated region. (C) IFAs of a stably expressed second copy of GRA24-Myc revealed that, in parasites lacking ASP5, this protein was no longer addressed to the host nucleus and instead accumulates within the PV. (D) GRA24-Myc, which is devoid of PEXEL-like sequence, shows a similar migration profile in both strains. For panel B and D, parasites were collected 24 hr post-infection. α-Catalase was used as a loading control.</p>", "links"=>[], "tags"=>["host cell remodelling", "host cell nucleus", "parasite", "ht", "bradyzoite cyst wall formation", "intravacuolar nanotubular network", "gra", "ASP 5 causes", "pvm", "gondii aspartyl protease 5", "motif", "parasitophorous vacuole membrane", "protein", "ASP 5"], "article_id"=>1577836, "categories"=>["Biological Sciences"], "users"=>["Pierre-Mehdi Hammoudi", "Damien Jacot", "Christina Mueller", "Manlio Di Cristina", "Sunil Kumar Dogga", "Jean-Baptiste Marq", "Julia Romano", "Nicolò Tosetti", "Juan Dubrot", "Yalin Emre", "Matteo Lunghi", "Isabelle Coppens", "Masahiro Yamamoto", "Daniel Sojka", "Paco Pino", "Dominique Soldati-Favre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005211.g004", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ASP5_deletion_compromises_the_export_of_GRA16_and_GRA24_beyond_the_PVM_/1577836", "title"=>"ASP5 deletion compromises the export of GRA16 and GRA24 beyond the PVM.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 02:58:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2362696"], "description"=>"<p>(A) In the absence of ASP5 in type I parasites, GRA1 staining was not affected. Conversely, while GRA2 labelling was still present at the PV, it displayed an altered, punctate signal when compared to wt parasites. More strikingly, in the absence of ASP5, GRA3, and GRA7 remained in the vacuolar space and were no longer inserted into the PVM. α-GAP45 antibodies were used to stain the parasite periphery. All IFAs were performed with PFA/GA fixation for 30 min. Scale bars represent 2 μm. (B) Electron micrographs of the membranous nanotubular network (MNN, black arrows) in type I parasites. Strikingly, parasites lacking ASP5 have either no MNN, or occasionally punctate structures (black asterisk) in the vacuolar space. In contrast, ASP5 deletion did not affect the overall ultrastructure of the parasites, particularly the presence of the dense granules (DG). (C) Electron micrographs of infected host cells (hc) showing host mitochondria (hm) association with the PV of <i>RH</i> and <i>RHΔasp5</i> parasites (p). Scale bars represent 1 μm.</p>", "links"=>[], "tags"=>["host cell remodelling", "host cell nucleus", "parasite", "ht", "bradyzoite cyst wall formation", "intravacuolar nanotubular network", "gra", "ASP 5 causes", "pvm", "gondii aspartyl protease 5", "motif", "parasitophorous vacuole membrane", "protein", "ASP 5"], "article_id"=>1577833, "categories"=>["Biological Sciences"], "users"=>["Pierre-Mehdi Hammoudi", "Damien Jacot", "Christina Mueller", "Manlio Di Cristina", "Sunil Kumar Dogga", "Jean-Baptiste Marq", "Julia Romano", "Nicolò Tosetti", "Juan Dubrot", "Yalin Emre", "Matteo Lunghi", "Isabelle Coppens", "Masahiro Yamamoto", "Daniel Sojka", "Paco Pino", "Dominique Soldati-Favre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005211.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_the_absence_of_ASP5_PV_architecture_but_not_host_organelle_recruitment_is_altered_/1577833", "title"=>"In the absence of ASP5, PV architecture but not host organelle recruitment is altered.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 02:58:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2362694"], "description"=>"<p>(A) In type I parasites, indirect immunofluorescence analyses (IFA) using α-Ty antibodies revealed that ASP5-3Ty is a Golgi-resident protein, which co-localizes with the Golgi marker GRASP-YFP. Gliding associated protein 45 (α-GAP45) antibodies were used to stain the parasite periphery. Scale bars represent 2 μm. (B) Western blots completed with α-Ty antibodies, revealed that ASP5-3Ty migrates at the molecular size of 100 kDa, but also as a second lower band of 55 kDa. No Ty signal was detected in <i>RHΔku80Δasp5</i> parasites. Complementation with ASP5-Ty gDNA (<i>asp5g-Ty</i>) restores the wt pattern while complementation with ASP5-Ty cDNA (<i>asp5c-Ty</i>) leads only to production of the 100 kDa band. <i>T</i>. <i>gondii</i> Actin 1 (α-ACT1) was used as a loading control. (C) In type II parasites, ASP5-3Ty migrates similarly to that seen in type I parasites, with two bands detected at 100 and 55 kDa. No Ty signal was detected for <i>PRUΔku80Δasp5</i> parasites. Detection of α-ACT1 was used as a loading control. (D) Intracellular growth type I and type II parasites was assessed after 24 hr in complete media. Parasites lacking ASP5 were not impacted in their ability to replicate intracellularly. Data are mean value ± s.d. of three independent experiments. (E) Deletion of ASP5 resulted in a significant impairment of the lytic cycle, as assessed by plaque formation after 7 days, in both type I and II parasites. Complementation with ASP5-Ty gDNA (<i>asp5g-Ty)</i> fully restored plaque formation whereas complementation with ASP5-Ty cDNA (<i>asp5c-Ty)</i> led to an intermediate plaque phenotype. (F) Mean area of 10 plaques ± s.d.is depicted. (G) Quantification of BIPPO-stimulated egressed vacuoles. Data show mean ± s.d. of three independent experiments. (H) During natural egress, a significant fraction of the parasites remains trapped either inside the parasitophorous vacuole or the host plasma membrane which resemble detached sphere-like structures. No other apparent phenotype was observed.</p>", "links"=>[], "tags"=>["host cell remodelling", "host cell nucleus", "parasite", "ht", "bradyzoite cyst wall formation", "intravacuolar nanotubular network", "gra", "ASP 5 causes", "pvm", "gondii aspartyl protease 5", "motif", "parasitophorous vacuole membrane", "protein", "ASP 5"], "article_id"=>1577831, "categories"=>["Biological Sciences"], "users"=>["Pierre-Mehdi Hammoudi", "Damien Jacot", "Christina Mueller", "Manlio Di Cristina", "Sunil Kumar Dogga", "Jean-Baptiste Marq", "Julia Romano", "Nicolò Tosetti", "Juan Dubrot", "Yalin Emre", "Matteo Lunghi", "Isabelle Coppens", "Masahiro Yamamoto", "Daniel Sojka", "Paco Pino", "Dominique Soldati-Favre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005211.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ASP5_is_a_dispensable_Golgi_resident_protein_/1577831", "title"=>"ASP5 is a dispensable Golgi-resident protein.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 02:58:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2362724"], "description"=>"<p>(A) Schematic representation of a host cell infected by either type I or type II tachyzoites. In a wt situation (left panel), intracellular tachyzoites reside within an MNN containing PV. During intracellular development, dense granule proteins are delivered either to the vacuolar space, the PVM, or are addressed to the host cell cytosol and nucleus. Intriguingly, the absence of ASP5 (right panel) does not affect the secretion of the dense granules, and accordingly, PEXEL-like and non-PEXEL-like motif-containing proteins are still delivered to the PV. However, ASP5 deletion leads to the disappearance of the MNN, altered localization of some PV- and PVM-resident GRAs, and to the PV-accumulation of proteins normally exported to the host cell cytosol. Accordingly, the overall infected host cell transcription profile response is significantly different in <i>Δasp5</i> parasites infection. The accumulation of some exported GRAs in the PV suggests that the export machinery used to cross the PVM is affected upon ASP5 deletion. In contrast, no significant effect was observed for early host organelle recruitment to the PVM, but only a reduced fusion of host mitochondria was observed. Specifically in type I parasites, blocking of IRG recruitment is unaffected. SAG1 is a tachyzoite marker. (B) Differentiation in bradyzoites is not affected by ASP5 deletion but parasites fail to form a cyst wall. SAG4 and BAG1 are bradyzoite markers.</p>", "links"=>[], "tags"=>["host cell remodelling", "host cell nucleus", "parasite", "ht", "bradyzoite cyst wall formation", "intravacuolar nanotubular network", "gra", "ASP 5 causes", "pvm", "gondii aspartyl protease 5", "motif", "parasitophorous vacuole membrane", "protein", "ASP 5"], "article_id"=>1577859, "categories"=>["Biological Sciences"], "users"=>["Pierre-Mehdi Hammoudi", "Damien Jacot", "Christina Mueller", "Manlio Di Cristina", "Sunil Kumar Dogga", "Jean-Baptiste Marq", "Julia Romano", "Nicolò Tosetti", "Juan Dubrot", "Yalin Emre", "Matteo Lunghi", "Isabelle Coppens", "Masahiro Yamamoto", "Daniel Sojka", "Paco Pino", "Dominique Soldati-Favre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005211.g009", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stage_specific_functions_of_ASP5_in_T_gondii_/1577859", "title"=>"Stage specific functions of ASP5 in <i>T</i>. <i>gondii</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 02:58:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2362702"], "description"=>"<p>(A-B) C57Bl/6 mice were inoculated by intraperitoneal injection of 5.10<sup>1</sup> or 5.10<sup>3</sup> (A) type I parasite, and 10<sup>5</sup> or 10<sup>6</sup> (B) for type II parasites. Mice survival was monitored over time. Five animals were infected for each experiment.</p>", "links"=>[], "tags"=>["host cell remodelling", "host cell nucleus", "parasite", "ht", "bradyzoite cyst wall formation", "intravacuolar nanotubular network", "gra", "ASP 5 causes", "pvm", "gondii aspartyl protease 5", "motif", "parasitophorous vacuole membrane", "protein", "ASP 5"], "article_id"=>1577839, "categories"=>["Biological Sciences"], "users"=>["Pierre-Mehdi Hammoudi", "Damien Jacot", "Christina Mueller", "Manlio Di Cristina", "Sunil Kumar Dogga", "Jean-Baptiste Marq", "Julia Romano", "Nicolò Tosetti", "Juan Dubrot", "Yalin Emre", "Matteo Lunghi", "Isabelle Coppens", "Masahiro Yamamoto", "Daniel Sojka", "Paco Pino", "Dominique Soldati-Favre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005211.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ASP5_deletion_affects_in_vivo_virulence_of_type_I_and_type_II_parasites_/1577839", "title"=>"ASP5 deletion affects <i>in vivo</i> virulence of type I and type II parasites.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 02:58:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2362802", "https://ndownloader.figshare.com/files/2362803", "https://ndownloader.figshare.com/files/2362804", "https://ndownloader.figshare.com/files/2362805", "https://ndownloader.figshare.com/files/2362806", "https://ndownloader.figshare.com/files/2362807", "https://ndownloader.figshare.com/files/2362808", "https://ndownloader.figshare.com/files/2362809", "https://ndownloader.figshare.com/files/2362810"], "description"=>"<div><p><i>Toxoplasma gondii</i> possesses sets of dense granule proteins (GRAs) that either assemble at, or cross the parasitophorous vacuole membrane (PVM) and exhibit motifs resembling the HT/PEXEL previously identified in a repertoire of exported <i>Plasmodium</i> proteins. Within <i>Plasmodium spp</i>., cleavage of the HT/PEXEL motif by the endoplasmic reticulum-resident protease Plasmepsin V precedes trafficking to and export across the PVM of proteins involved in pathogenicity and host cell remodelling. Here, we have functionally characterized the <i>T</i>. <i>gondii</i> aspartyl protease 5 (ASP5), a Golgi-resident protease that is phylogenetically related to Plasmepsin V. We show that deletion of <i>ASP5</i> causes a significant loss in parasite fitness <i>in vitro</i> and an altered virulence <i>in vivo</i>. Furthermore, we reveal that ASP5 is necessary for the cleavage of GRA16, GRA19 and GRA20 at the PEXEL-like motif. In the absence of ASP5, the intravacuolar nanotubular network disappears and several GRAs fail to localize to the PVM, while GRA16 and GRA24, both known to be targeted to the host cell nucleus, are retained within the vacuolar space. Additionally, hypermigration of dendritic cells and bradyzoite cyst wall formation are impaired, critically impacting on parasite dissemination and persistence. Overall, the absence of ASP5 dramatically compromises the parasite’s ability to modulate host signalling pathways and immune responses.</p></div>", "links"=>[], "tags"=>["host cell remodelling", "host cell nucleus", "parasite", "ht", "bradyzoite cyst wall formation", "intravacuolar nanotubular network", "gra", "ASP 5 causes", "pvm", "gondii aspartyl protease 5", "motif", "parasitophorous vacuole membrane", "protein", "ASP 5"], "article_id"=>1577899, "categories"=>["Biological Sciences"], "users"=>["Pierre-Mehdi Hammoudi", "Damien Jacot", "Christina Mueller", "Manlio Di Cristina", "Sunil Kumar Dogga", "Jean-Baptiste Marq", "Julia Romano", "Nicolò Tosetti", "Juan Dubrot", "Yalin Emre", "Matteo Lunghi", "Isabelle Coppens", "Masahiro Yamamoto", "Daniel Sojka", "Paco Pino", "Dominique Soldati-Favre"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005211.s001", "https://dx.doi.org/10.1371/journal.ppat.1005211.s002", "https://dx.doi.org/10.1371/journal.ppat.1005211.s003", "https://dx.doi.org/10.1371/journal.ppat.1005211.s004", "https://dx.doi.org/10.1371/journal.ppat.1005211.s005", "https://dx.doi.org/10.1371/journal.ppat.1005211.s006", "https://dx.doi.org/10.1371/journal.ppat.1005211.s007", "https://dx.doi.org/10.1371/journal.ppat.1005211.s008", "https://dx.doi.org/10.1371/journal.ppat.1005211.s009"], "stats"=>{"downloads"=>8, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Fundamental_Roles_of_the_Golgi_Associated_Toxoplasma_Aspartyl_Protease_ASP5_at_the_Host_Parasite_Interface/1577899", "title"=>"Fundamental Roles of the Golgi-Associated <i>Toxoplasma</i> Aspartyl Protease, ASP5, at the Host-Parasite Interface", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-10-16 02:58:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2362697"], "description"=>"<p>(A) Type I parasites were transiently transfected with GRA19-HA, GRA19-HA-R124A (PEXEL-like mutant control) or GRA20-HA. Intracellular parasites were collected and analysed by western blot. In the absence of ASP5, processing of GRA19-HA and GRA20-HA was abolished as detected by α-HA antibodies. Middle gel represents a longer exposure. α-Catalase antibodies were used as a loading control. (B) IFAs of parasites transiently transfected with GRA19-HA and GRA20-HA as presented in (A). The absence of the ASP5-dependent processing of GRA20 did not affect its localization at the PVM. Scale bars represent 2 μm. (C) Dense granule secretion assays in type I parasites revealed that deletion of ASP5 does not impair GRA1, 3 or 7 secretion. Interestingly, the multiple band pattern of GRA7 is abolished under these conditions. Catalase and MIC2 (micronemal protein 2) were used as controls for the non-secreted and secreted fraction respectively (MIC2 is processed upon secretion of the micronemes). ESA: excretory secretory antigens.</p>", "links"=>[], "tags"=>["host cell remodelling", "host cell nucleus", "parasite", "ht", "bradyzoite cyst wall formation", "intravacuolar nanotubular network", "gra", "ASP 5 causes", "pvm", "gondii aspartyl protease 5", "motif", "parasitophorous vacuole membrane", "protein", "ASP 5"], "article_id"=>1577834, "categories"=>["Biological Sciences"], "users"=>["Pierre-Mehdi Hammoudi", "Damien Jacot", "Christina Mueller", "Manlio Di Cristina", "Sunil Kumar Dogga", "Jean-Baptiste Marq", "Julia Romano", "Nicolò Tosetti", "Juan Dubrot", "Yalin Emre", "Matteo Lunghi", "Isabelle Coppens", "Masahiro Yamamoto", "Daniel Sojka", "Paco Pino", "Dominique Soldati-Favre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005211.g003", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ASP5_mediates_the_cleavage_of_PEXEL_like_motif_containing_proteins_but_does_not_impact_on_dense_granule_secretion_/1577834", "title"=>"ASP5 mediates the cleavage of PEXEL-like motif-containing proteins but does not impact on dense granule secretion.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 02:58:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2362710"], "description"=>"<p>(A) Cell track analyses of DCs were assessed 6–8 hr post-infection for each condition. Circles represent average speed (μm/min) ± s.d. of 100 single cells measured during 45 min from one representative experiment (*<i>P</i><0.01, Student’s <i>t</i>-test). (B) Transmigration of DCs was assessed in a transwell system +/- CCL19 16 hr post-infection with either type I or type II parasites. CCL19 induction resulted in the transmigration of wt or complemented parasites whereas in <i>Δasp5</i> strains, transmigration was reduced almost to the same level as the non-induced samples. The graph shows one representative condition ± s.d. from three independent biological replicates (*<i>P</i><0.01, Student’s <i>t</i>-test).</p>", "links"=>[], "tags"=>["host cell remodelling", "host cell nucleus", "parasite", "ht", "bradyzoite cyst wall formation", "intravacuolar nanotubular network", "gra", "ASP 5 causes", "pvm", "gondii aspartyl protease 5", "motif", "parasitophorous vacuole membrane", "protein", "ASP 5"], "article_id"=>1577848, "categories"=>["Biological Sciences"], "users"=>["Pierre-Mehdi Hammoudi", "Damien Jacot", "Christina Mueller", "Manlio Di Cristina", "Sunil Kumar Dogga", "Jean-Baptiste Marq", "Julia Romano", "Nicolò Tosetti", "Juan Dubrot", "Yalin Emre", "Matteo Lunghi", "Isabelle Coppens", "Masahiro Yamamoto", "Daniel Sojka", "Paco Pino", "Dominique Soldati-Favre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005211.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ASP5_affects_dendritic_cell_DCs_transmigration_but_not_hypermotility_/1577848", "title"=>"ASP5 affects dendritic cell (DCs) transmigration but not hypermotility.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 02:58:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2362727"], "description"=>"<p>*Strains not generated in this study; DSB: double strand break; aa: amino acid</p><p><i>T</i>. <i>gondii</i> strains used and developed in this study.</p>", "links"=>[], "tags"=>["host cell remodelling", "host cell nucleus", "parasite", "ht", "bradyzoite cyst wall formation", "intravacuolar nanotubular network", "gra", "ASP 5 causes", "pvm", "gondii aspartyl protease 5", "motif", "parasitophorous vacuole membrane", "protein", "ASP 5"], "article_id"=>1577861, "categories"=>["Biological Sciences"], "users"=>["Pierre-Mehdi Hammoudi", "Damien Jacot", "Christina Mueller", "Manlio Di Cristina", "Sunil Kumar Dogga", "Jean-Baptiste Marq", "Julia Romano", "Nicolò Tosetti", "Juan Dubrot", "Yalin Emre", "Matteo Lunghi", "Isabelle Coppens", "Masahiro Yamamoto", "Daniel Sojka", "Paco Pino", "Dominique Soldati-Favre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005211.t001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_T_gondii_strains_used_and_developed_in_this_study_/1577861", "title"=>"<i>T</i>. <i>gondii</i> strains used and developed in this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-10-16 02:58:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/2362706"], "description"=>"<p>(A) Interferon-γ stimulated, bone marrow derived macrophages (BMDMs) were infected with type I and type II parasite lines for 1 hr at a MOI of 1. In the absence of ASP5, type I parasites were not affected in IRG recruitment to the PVM. Type II parasites were used as controls. Parasites were labelled with α-GRA2, host IRGs with α-Irgb6 antibodies, and host nuclei with DAPI. IFAs are representative data from three independent biological experiments. Scale bars represent 2 μm. (B) IL-12p40 levels were measured by ELISA from supernatant collected 40 hr after BMDM infection with type I and type II strain parasites. Supernatant from uninfected cells was used as a control (u.i.). In both types, the absence of ASP5 dramatically reduces IL-12p40 levels. Data are mean value ± s.d. of three independent experiments. (*<i>P</i><0.01, **<i>P</i><0.005, Student’s <i>t</i>-test). (C) Quantitative chemokine production was determined by qRT-PCR on mouse embryonic fibroblast (pMEFs) infected with type I and type II parasites. Values were normalized to the amount of actin in each sample. Data are mean value ± s.d. of three independent experiments. (*<i>P</i><0.01, **<i>P</i><0.05, Student’s <i>t</i>-test). (D) Following KEGG analysis of the differentially expressed genes (>2 fold, p-value < 0.05) between parental and <i>Δasp5</i> infected BMDMs, heatmaps were generated with genes selected from representative KEGG pathways. (Red: low, Green: high). Both up- and down-regulated genes of the host cell were analyzed together.</p>", "links"=>[], "tags"=>["host cell remodelling", "host cell nucleus", "parasite", "ht", "bradyzoite cyst wall formation", "intravacuolar nanotubular network", "gra", "ASP 5 causes", "pvm", "gondii aspartyl protease 5", "motif", "parasitophorous vacuole membrane", "protein", "ASP 5"], "article_id"=>1577843, "categories"=>["Biological Sciences"], "users"=>["Pierre-Mehdi Hammoudi", "Damien Jacot", "Christina Mueller", "Manlio Di Cristina", "Sunil Kumar Dogga", "Jean-Baptiste Marq", "Julia Romano", "Nicolò Tosetti", "Juan Dubrot", "Yalin Emre", "Matteo Lunghi", "Isabelle Coppens", "Masahiro Yamamoto", "Daniel Sojka", "Paco Pino", "Dominique Soldati-Favre"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005211.g006", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ASP5_modulates_host_innate_immune_responses_/1577843", "title"=>"ASP5 modulates host innate immune responses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-16 02:58:42"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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