title: Sorting nexin 3 (SNX3) is a component of a tubular endosomal network induced by Salmonella and involved in maturation of the Salmonella-containing vacuole.
abstract: Salmonella enterica serovar Typhimurium is an intracellular pathogen that grows within a modified endomembrane compartment, the Salmonella-containing vacuole (SCV). Maturation of nascent SCVs involves the recruitment of early endosome markers and the remodelling of phosphoinositides at the membrane of the vacuole, in particular the production of phosphatidylinositol 3-phosphate [PI(3)P]. Sorting nexins (SNXs) are a family of proteins characterized by the presence of a phox homology (PX) domain that binds to phosphoinositides and are involved in intracellular trafficking in eukaryotic cells. We therefore studied whether sorting nexins, particularly sorting nexin 3 (SNX3), play a role in Salmonella infection. We found that SNX3 transiently localized to SCVs at early times post invasion (10 min) and presented a striking tubulation phenotype in the vicinity of SCVs at later times (30-60 min). The bacterial effector SopB, which is known to promote PI(3)P production on SCVs, was required for the formation of SNX3 tubules. In addition, RAB5 was also required for the formation of SNX3 tubules. Depletion of SNX3 by siRNA impaired RAB7 and LAMP1 recruitment to the SCV. Moreover, the formation of Salmonella-induced filaments (Sifs) was altered by SNX3 knock-down. Therefore, SNX3 plays a significant role in regulating the maturation of SCVs.
authors.affiliation: Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada M5G1X8.
authors.forename: Virginie
authors.initials: V
authors.lastname: Braun
authors.forename: Anthony
authors.initials: A
authors.lastname: Wong
authors.forename: Marija
authors.initials: M
authors.lastname: Landekic
authors.forename: Wan Jin
authors.initials: WJ
authors.lastname: Hong
authors.forename: Sergio
authors.initials: S
authors.lastname: Grinstein
authors.forename: John H
authors.initials: JH
authors.lastname: Brumell
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology; D002460:Cell Line; D004285:Dogs; D011992:Endosomes / Q000378:metabolism* / Q000382:microbiology; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D012480:Salmonella Infections / Q000378:metabolism / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D058305:Sorting Nexins / Q000378:metabolism / Q000502:physiology*; D014774:Virulence; D020696:rab5 GTP-Binding Proteins / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; C513980:SNX3 protein, human; D058305:Sorting Nexins; C489224:SopB protein, Salmonella; D020696:rab5 GTP-Binding Proteins