title: Ubiquitination of Innate Immune Regulator TRAF3 Orchestrates Expulsion of Intracellular Bacteria by Exocyst Complex.
abstract: Although the intracellular trafficking system is integral to most physiologic activities, its role in mediating immune responses to infection has remained elusive. Here, we report that infected bladder epithelial cells (BECs) mobilized the exocyst complex, a powerful exporter of subcellular vesicles, to rapidly expel intracellular bacteria back for clearance. Toll-like receptor (TLR) 4 signals emanating from bacteria-containing vesicles (BCVs) were found to trigger K33-linked polyubiquitination of TRAF3 at Lys168, which was then detected by RalGDS, a guanine nucleotide exchange factor (GEF) that precipitated the assembly of the exocyst complex. Although this distinct modification of TRAF3 served to connect innate immune signaling to the cellular trafficking apparatus, it crucially ensured temporal and spatial accuracy in determining which among the many subcellular vesicles was recognized and selected for expulsion in response to innate immune signaling.
authors.affiliation: Department of Molecular Genetics & Microbiology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: ymiao@rockefeller.edu.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jianxuan
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Molecular Genetics & Microbiology, Duke University Medical Center, Durham, NC 27710, USA; Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA; Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore 169857, Singapore.
authors.forename: Soman N
authors.initials: SN
authors.lastname: Abraham
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology*; D005089:Exocytosis; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D042541:Intracellular Space; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D048008:TNF Receptor-Associated Factor 3 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics; D022161:Transport Vesicles / Q000378:metabolism*; D054875:Ubiquitination; D001743:Urinary Bladder / Q000382:microbiology / Q000473:pathology*; D014552:Urinary Tract Infections / Q000276:immunology*; D019459:Urothelium / Q000276:immunology* / Q000382:microbiology; D020726:ral Guanine Nucleotide Exchange Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D048008:TNF Receptor-Associated Factor 3; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D020726:ral Guanine Nucleotide Exchange Factor