title: Antibacterial autophagy occurs at PI(3)P-enriched domains of the endoplasmic reticulum and requires Rab1 GTPase.
abstract: Autophagy mediates the degradation of cytoplasmic components in eukaryotic cells and plays a key role in immunity. The mechanism of autophagosome formation is not clear. Here we examined two potential membrane sources for antibacterial autophagy: the ER and mitochondria. DFCP1, a marker of specialized ER domains known as 'omegasomes,' associated with Salmonella-containing autophagosomes via its PtdIns(3)P and ER-binding domains, while a mitochondrial marker (cytochrome b5-GFP) did not. Rab1 also localized to autophagosomes, and its activity was required for autophagosome formation, clearance of protein aggregates and peroxisomes, and autophagy of Salmonella. Overexpression of Rab1 enhanced antibacterial autophagy. The role of Rab1 in antibacterial autophagy was independent of its role in ER-to-Golgi transport. Our data suggest that antibacterial autophagy occurs at omegasomes and reveal that the Rab1 GTPase plays a crucial role in mammalian autophagy.
authors.affiliation: Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Ju
authors.initials: J
authors.lastname: Huang
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Birmingham
authors.forename: Shahab
authors.initials: S
authors.lastname: Shahnazari
authors.forename: Jessica
authors.initials: J
authors.lastname: Shiu
authors.forename: Yiyu T
authors.initials: YT
authors.lastname: Zheng
authors.forename: Adam C
authors.initials: AC
authors.lastname: Smith
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Campellone
authors.forename: Won Do
authors.initials: WD
authors.lastname: Heo
authors.forename: Samantha
authors.initials: S
authors.lastname: Gruenheid
authors.forename: Tobias
authors.initials: T
authors.lastname: Meyer
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Welch
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Ktistakis
authors.forename: Peter Kijun
authors.initials: PK
authors.lastname: Kim
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Klionsky
authors.forename: John H
authors.initials: JH
authors.lastname: Brumell
mesh_terms: D000818:Animals; D001343:Autophagy; D002352:Carrier Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism; D010588:Phagosomes / Q000382:microbiology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D021381:Protein Transport / Q000187:drug effects; D012486:Salmonella typhimurium / Q000276:immunology*; D020123:Sirolimus / Q000494:pharmacology; D057149:Ubiquitinated Proteins / Q000737:chemistry; D020761:rab1 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D018129:Phosphatidylinositol Phosphates; D057149:Ubiquitinated Proteins; C426003:ZFYVE1 protein, human; C055525:phosphatidylinositol 3-phosphate; D020761:rab1 GTP-Binding Proteins; D020123:Sirolimus