title: TBC1D5 and the AP2 complex regulate ATG9 trafficking and initiation of autophagy.
abstract: The RabGAP protein TBC1D5 controls cellular endomembrane trafficking processes and binds the retromer subunit VPS29 and the ubiquitin-like protein ATG8 (LC3). Here, we describe that TBC1D5 also associates with ATG9 and the active ULK1 complex during autophagy. Moreover, ATG9 and TBC1D5 interact with clathrin and the AP2 complex. Depletion of TBC1D5 leads to missorting of ATG9 to late endosomes upon activation of autophagy, whereas inhibition of clathrin-mediated endocytosis or AP2 depletion alters ATG9 trafficking and its association with TBC1D5. Taken together, our data show that TBC1D5 and the AP2 complex are important novel regulators of the rerouting of ATG9-containing vesicular carriers toward sites of autophagosome formation.
authors.affiliation: Buchmann Institute for Molecular Life Sciences (BMLS) and Institute of Biochemistry II Goethe University School of Medicine, Frankfurt, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Popovic
authors.forename: Ivan
authors.initials: I
authors.lastname: Dikic
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000502:physiology*; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog; D000071183:Autophagy-Related Proteins; D045744:Cell Line, Tumor; D004705:Endocytosis; D020690:GTPase-Activating Proteins / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport
chemical_list: C503283:ATG9B protein, human; D033962:Adaptor Protein Complex 2; D000071183:Autophagy-Related Proteins; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C543487:TBC1D5 protein, human; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C484754:ULK1 protein, human