title: Expression of a ULK1/2 binding-deficient ATG13 variant can partially restore autophagic activity in ATG13-deficient cells.
abstract: Autophagy describes an intracellular process responsible for the lysosome-dependent degradation of cytosolic components. The ULK1/2 complex comprising the kinase ULK1/2 and the accessory proteins ATG13, RB1CC1, and ATG101 has been identified as a central player in the autophagy network, and it represents the main entry point for autophagy-regulating kinases such as MTOR and AMPK. It is generally accepted that the ULK1 complex is constitutively assembled independent of nutrient supply. Here we report the characterization of the ATG13 region required for the binding of ULK1/2. This binding site is established by an extremely short peptide motif at the C terminus of ATG13. This motif is mandatory for the recruitment of ULK1 into the autophagy-initiating high-molecular mass complex. Expression of a ULK1/2 binding-deficient ATG13 variant in ATG13-deficient cells resulted in diminished but not completely abolished autophagic activity. Collectively, we propose that autophagy can be executed by mechanisms that are dependent or independent of the ULK1/2-ATG13 interaction.
authors.affiliation: a Institute of Molecular Medicine I; Heinrich-Heine-University ; Düsseldorf , Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Hieke
authors.affiliation: a Institute of Molecular Medicine I; Heinrich-Heine-University ; Düsseldorf , Germany.
authors.forename: Antje S
authors.initials: AS
authors.lastname: Löffler
authors.affiliation: b Department of Biochemistry and Molecular Biology ; Graduate School and Faculty of Medicine; University of Tokyo ; Tokyo , Japan.|c Department of Physiology and cell Biology ; Tokyo Medical and Dental University ; Tokyo , Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaizuka
authors.affiliation: a Institute of Molecular Medicine I; Heinrich-Heine-University ; Düsseldorf , Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Berleth
authors.affiliation: a Institute of Molecular Medicine I; Heinrich-Heine-University ; Düsseldorf , Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Böhler
authors.affiliation: a Institute of Molecular Medicine I; Heinrich-Heine-University ; Düsseldorf , Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Drießen
authors.affiliation: a Institute of Molecular Medicine I; Heinrich-Heine-University ; Düsseldorf , Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Stuhldreier
authors.affiliation: a Institute of Molecular Medicine I; Heinrich-Heine-University ; Düsseldorf , Germany.
authors.forename: Olena
authors.initials: O
authors.lastname: Friesen
authors.affiliation: d Center for Microbial Pathogenesis; The Research Institute at Nationwide Children's Hospital ; Columbus , OH USA.
authors.forename: Kaivon
authors.initials: K
authors.lastname: Assani
authors.affiliation: a Institute of Molecular Medicine I; Heinrich-Heine-University ; Düsseldorf , Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schmitz
authors.affiliation: a Institute of Molecular Medicine I; Heinrich-Heine-University ; Düsseldorf , Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Peter
authors.affiliation: e Department of Dermatology ; Medical Center; ZBSA Center for Biological Systems Analysis; BIOSS Centre for Biological Signaling Studies; Freiburg Institute for Advanced Studies; University of Freiburg ; Freiburg , Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Diedrich
authors.affiliation: e Department of Dermatology ; Medical Center; ZBSA Center for Biological Systems Analysis; BIOSS Centre for Biological Signaling Studies; Freiburg Institute for Advanced Studies; University of Freiburg ; Freiburg , Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Dengjel
authors.affiliation: f Institute of Basic Medical Sciences; Faculty of Medicine; University of Oslo ; Oslo , Norway.
authors.forename: Petter
authors.initials: P
authors.lastname: Holland
authors.affiliation: f Institute of Basic Medical Sciences; Faculty of Medicine; University of Oslo ; Oslo , Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Simonsen
authors.affiliation: a Institute of Molecular Medicine I; Heinrich-Heine-University ; Düsseldorf , Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wesselborg
authors.affiliation: b Department of Biochemistry and Molecular Biology ; Graduate School and Faculty of Medicine; University of Tokyo ; Tokyo , Japan.|c Department of Physiology and cell Biology ; Tokyo Medical and Dental University ; Tokyo , Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Mizushima
authors.affiliation: a Institute of Molecular Medicine I; Heinrich-Heine-University ; Düsseldorf , Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Stork
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog; D004795:Enzyme Stability; D005347:Fibroblasts / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation; D010455:Peptides / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D059748:Proteolysis; D000071456:Sequestosome-1 Protein
chemical_list: C000608442:ATG13 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D006360:Heat-Shock Proteins; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D010455:Peptides; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; C401061:Ulk2 protein, mouse; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C112444:Ulk1 protein, mouse
keywords: ATG101; ATG13; RB1CC1; ULK1; autophagy