title: An essential role for the ATG8 ortholog LC3C in antibacterial autophagy.
abstract: Autophagy defends the mammalian cytosol against bacterial invasion. Efficient bacterial engulfment by autophagy requires cargo receptors that bind (a) homolog(s) of the ubiquitin-like protein Atg8 on the phagophore membrane. The existence of multiple ATG8 orthologs in higher eukaryotes suggests that they may perform distinct functions. However, no specific role has been assigned to any mammalian ATG8 ortholog. We recently discovered that the autophagy receptor CALCOCO2/NDP52, which detects cytosol-invading Salmonella enterica serovar Typhimurium (S. Typhimurium), preferentially binds LC3C. The CALCOCO2/NDP52-LC3C interaction is essential for cell-autonomous immunity against cytosol-exposed S. Typhimurium, because cells lacking either protein fail to target bacteria into the autophagy pathway. The selectivity of CALCOCO2/NDP52 for LC3C is determined by a novel LC3C interacting region (CLIR), in which the lack of the key aromatic residue of canonical LIRs is compensated by LC3C-specific interactions. Our findings provide a new layer of regulation to selective autophagy, suggesting that specific interactions between autophagy receptors and the ATG8 orthologs are of biological importance.
authors: MRC Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge, UK.
authors: Natalia
authors: N
authors: von Muhlinen
authors: Masato
authors: M
authors: Akutsu
authors: Benjamin J
authors: BJ
authors: Ravenhill
authors: Ágnes
authors: Á
authors: Foeglein
authors: Stuart
authors: S
authors: Bloor
authors: Trevor J
authors: TJ
authors: Rutherford
authors: Stefan M V
authors: SM
authors: Freund
authors: David
authors: D
authors: Komander
authors: Felix
authors: F
authors: Randow
mesh_terms: D001343:Autophagy; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D012486:Salmonella typhimurium / Q000254:growth & development / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins
keywords: ATG8/LC3; LC3C; LIR; NDP52; Salmonella; autophagy