title: The ubiquitin-binding adaptor proteins p62/SQSTM1 and NDP52 are recruited independently to bacteria-associated microdomains to target Salmonella to the autophagy pathway.
abstract: Autophagy is an innate immune defense against bacterial invasion. Recent studies show that two adaptor proteins, p62 and NDP52, are required for autophagy of the bacterial pathogen Salmonella enterica serovar Typhimurium (S. typhimurium). However, it is not known why two different adaptors are required to target the same bacterial cargo to autophagy. Here we show that both adaptors are recruited to bacteria with similar kinetics, that they are recruited to bacteria independently of each other, and that depletion of either adaptor leads to impairment of antibacterial autophagy. Depletion of both adaptors does not synergistically impair autophagy, indicating they act in the same pathway. Remarkably, we observed that these adaptors do not colocalize, but rather form non-overlapping microdomains surrounding bacteria. We conclude that p62 and NDP52 act cooperatively to drive efficient antibacterial autophagy by targeting the protein complexes they coordinate to distinct micro-domains associated with bacteria.
authors.affiliation: Cell Biology Program, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Marija
authors.initials: M
authors.lastname: Cemma
authors.forename: Peter Kijun
authors.initials: PK
authors.lastname: Kim
authors.forename: John Hunter
authors.initials: JH
authors.lastname: Brumell
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001343:Autophagy; D002451:Cell Compartmentation; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D012475:Salmonella / Q000378:metabolism*; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C094297:CALCOCO2 protein, human; D009687:Nuclear Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D025801:Ubiquitin