FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2199866820> ?p ?o ?g. }

• W2199866820 abstract "Salmonella enterica serovar Typhimurium (S. Typhimurium) can invade non- phagocytic epithelial cells by injecting virulence factors into the host cell via a type III secretion system (T3SS) to induce macropinocytosis. However, the precise molecular processes that lead to this uptake are currently unknown. In this thesis I show that several sorting nexin (SNX) proteins, i.e. SNX18, SNX20 and SNX21, are involved in Salmonella invasion and examined their molecular action during this process. First I demonstrated that after docking at the plasma membrane S. Typhimurium triggers rapid translocation of cytosolic SNX18, a SH3-PX-BAR domain sorting nexin protein, to the bacteria-induced membrane ruffles and to the nascent Salmonella-containing vacuole (SCV). SNX18 recruitment required the inositol- phosphatase activity of the Salmonella T3SS effector SopB and an intact phosphoinositide-binding site within the PX domain of SNX18, but occurred independently of Rho-GTPases Rac1 and Cdc42 activation. I also demonstrate that SNX18 promotes formation of the SCV from the plasma membrane by acting as a scaffold to recruit Dynamin-2 and N-WASP in a process dependent on the SH3 domain of SNX18. Quantification of bacteria uptake revealed that overexpression of the full-length SNX18 increased the efficiency of bacteria internalization, whereas a decrease was detected in cells overexpressing the phosphoinositide-binding mutant R303Q, the DSH3 mutant, and in cells where endogenous levels of SNX18 were knocked-down by shRNA. This study identifies SNX18 as a novel target of SopB and suggests a mechanism where S. Typhimurium engages host factors via local manipulation of phosphoinositide composition at the site of invasion to orchestrate the internalization process. Secondly, I investigated the molecular details of SNX18 recruitment to the plasma membrane during the Salmonella invasion process. As we identified a significant cytosolic pool of SNX18 which can translocate to the site of S. Typhimurium invasion, we hypothesized that cytosolic SNX18 represents a closed auto-inhibited form where the N-terminal SH3 domain and adjacent low complexity (LC) region fold back onto the C-terminal PX-BAR domains. The cytosolic SNX18 required a conformational change into an open form, exposing the phosphoinositide-binding site for interaction with membrane. We also show that the bacteria-induced translocation of SNX18 is necessary but not sufficient for transient SNX18 phosphorylation. The LC domain of SNX18 functions in maintenance of the cytosol/membrane equilibrium of the protein and contains a not yet specified kinase binding motif and/or phosphosite(s). Screen for novel SNX18-specific interaction partners identified a- actinin-4 (ACTN4), a potential regulator for macropinocytosis and pathogen invasion as well. Though ACTN4 is recruited to the Salmonella induced ruffles, its recruitment is independent from SNX18 recruitment. And Akt translocation and phosphorylation induced by Salmonella invasion does not rely on SNX18 or ACTN4. Above all, this chapter provides an insight into the role of SNX18 as a scaffolding protein involved in plasma membrane remodeling and into manipulation of this process by bacterial pathogen. Finally, I commenced characterization of another SNX subfamily that contains SNX20 and SNX21 as potential regulators of Salmonella invasion. The study found that SNX20 and SNX21 localized to early endosomes in mammalian cells and the intact phosphoinositide-binding site in the PX domain is necessary for the localisation. S. Typhimurium could also recruit both SNX20 and SNX21 to the newly formed SCVs. However, live cell imaging demonstrated that the association between SNX20 or SNX21 with endosomes or SCVs is very transient. This suggested a role of SNX20 and SNX21 in early time points of endocytic process and pathogen internalization and vacuole maturation." @default.
• W2199866820 created "2016-06-24" @default.
• W2199866820 creator A5072570123 @default.
• W2199866820 date "2015-11-18" @default.
• W2199866820 modified "2023-09-27" @default.
• W2199866820 title "The role of sorting nexins in macropinocytosis and Salmonella invasion" @default.
• W2199866820 doi "https://doi.org/10.14264/uql.2015.1022" @default.
• W2199866820 hasPublicationYear "2015" @default.
• W2199866820 type Work @default.
• W2199866820 sameAs 2199866820 @default.
• W2199866820 citedByCount "0" @default.
• W2199866820 crossrefType "dissertation" @default.
• W2199866820 hasAuthorship W2199866820A5072570123 @default.
• W2199866820 hasConcept C102747710 @default.
• W2199866820 hasConcept C139770010 @default.
• W2199866820 hasConcept C1491633281 @default.
• W2199866820 hasConcept C156407911 @default.
• W2199866820 hasConcept C2778350249 @default.
• W2199866820 hasConcept C2779607309 @default.
• W2199866820 hasConcept C2781065037 @default.
• W2199866820 hasConcept C28005876 @default.
• W2199866820 hasConcept C51785407 @default.
• W2199866820 hasConcept C523546767 @default.
• W2199866820 hasConcept C54355233 @default.
• W2199866820 hasConcept C55493867 @default.
• W2199866820 hasConcept C79879829 @default.
• W2199866820 hasConcept C86803240 @default.
• W2199866820 hasConcept C95444343 @default.
• W2199866820 hasConceptScore W2199866820C102747710 @default.
• W2199866820 hasConceptScore W2199866820C139770010 @default.
• W2199866820 hasConceptScore W2199866820C1491633281 @default.
• W2199866820 hasConceptScore W2199866820C156407911 @default.
• W2199866820 hasConceptScore W2199866820C2778350249 @default.
• W2199866820 hasConceptScore W2199866820C2779607309 @default.
• W2199866820 hasConceptScore W2199866820C2781065037 @default.
• W2199866820 hasConceptScore W2199866820C28005876 @default.
• W2199866820 hasConceptScore W2199866820C51785407 @default.
• W2199866820 hasConceptScore W2199866820C523546767 @default.
• W2199866820 hasConceptScore W2199866820C54355233 @default.
• W2199866820 hasConceptScore W2199866820C55493867 @default.
• W2199866820 hasConceptScore W2199866820C79879829 @default.
• W2199866820 hasConceptScore W2199866820C86803240 @default.
• W2199866820 hasConceptScore W2199866820C95444343 @default.
• W2199866820 hasLocation W21998668201 @default.
• W2199866820 hasOpenAccess W2199866820 @default.
• W2199866820 hasPrimaryLocation W21998668201 @default.
• W2199866820 hasRelatedWork W19501297 @default.
• W2199866820 hasRelatedWork W1968245645 @default.
• W2199866820 hasRelatedWork W1987990206 @default.
• W2199866820 hasRelatedWork W1994983688 @default.
• W2199866820 hasRelatedWork W2024163184 @default.
• W2199866820 hasRelatedWork W2034772260 @default.
• W2199866820 hasRelatedWork W2035388947 @default.
• W2199866820 hasRelatedWork W2078264101 @default.
• W2199866820 hasRelatedWork W2105341630 @default.
• W2199866820 hasRelatedWork W2123105928 @default.
• W2199866820 hasRelatedWork W2125099638 @default.
• W2199866820 hasRelatedWork W2125663667 @default.
• W2199866820 hasRelatedWork W2155723410 @default.
• W2199866820 hasRelatedWork W2276073633 @default.
• W2199866820 hasRelatedWork W2607245752 @default.
• W2199866820 hasRelatedWork W2985227704 @default.
• W2199866820 hasRelatedWork W3001455775 @default.
• W2199866820 hasRelatedWork W3036254404 @default.
• W2199866820 hasRelatedWork W3141455887 @default.
• W2199866820 hasRelatedWork W3144365585 @default.
• W2199866820 isParatext "false" @default.
• W2199866820 isRetracted "false" @default.
• W2199866820 magId "2199866820" @default.
• W2199866820 workType "dissertation" @default.