title: NDP52, a novel autophagy receptor for ubiquitin-decorated cytosolic bacteria.
abstract: Autophagy functions as a cell-autonomous effector mechanism of innate immunity by separating bacteria from cytosolic resources and delivering them for lysosomal destruction. How cytosolic bacteria are targeted for autophagy is incompletely understood. We recently discovered that Salmonella enterica serotype Typhimurium and Streptococcus pyogenes are detected by NDP52 (nuclear dot protein 52 kDa), after these bacteria enter the cytosol of human cells and become decorated with polyubiquitinated proteins. NDP52 binds the bacterial ubiquitin coat as well as ATG8/LC3 and delivers cytosolic bacteria into autophagosomes. In the absence of NDP52 ubiquitin-coated bacteria accumulate outside ATG8/LC3(+) autophagosomes. Cells lacking NDP52 fail to restrict bacterial proliferation, as do cells depleted of TBK1, an IKK family kinase colocalizing with NDP52 at the bacterial surface. Our findings demonstrate the existence of a receptor for the selective autophagy of cytosolic bacteria, suggesting that cells are able to differentiate between antibacterial and other forms of autophagy.
authors.affiliation: MRC Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge, UK.
authors.forename: Natalia
authors.initials: N
authors.lastname: von Muhlinen
authors.forename: Teresa
authors.initials: T
authors.lastname: Thurston
authors.forename: Grigory
authors.initials: G
authors.lastname: Ryzhakov
authors.forename: Stuart
authors.initials: S
authors.lastname: Bloor
authors.forename: Felix
authors.initials: F
authors.lastname: Randow
mesh_terms: D001343:Autophagy / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012486:Salmonella typhimurium / Q000166:cytology / Q000378:metabolism*; D013297:Streptococcus pyogenes / Q000378:metabolism* / Q000648:ultrastructure; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: C094297:CALCOCO2 protein, human; D009687:Nuclear Proteins; D025801:Ubiquitin; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human