title: Receptor-Bound Targets of Selective Autophagy Use a Scaffold Protein to Activate the Atg1 Kinase.
abstract: Selective autophagy eliminates protein aggregates, damaged organelles, and other targets that otherwise accumulate and cause disease. Autophagy receptors mediate selectivity by connecting targets to the autophagosome membrane. It has remained unknown whether receptors perform additional functions. Here, we show that in yeast certain receptor-bound targets activate Atg1, the kinase that controls autophagosome formation. Specifically, we found that in nutrient-rich conditions, Atg1 is active only in a multisubunit complex comprising constitutive protein aggregates, their autophagy receptor, and a scaffold protein, Atg11. Development of a cell-free assay for Atg1-mediated phosphorylation enabled us to activate Atg1 with purified receptor-bound aggregates and Atg11. Another target, damaged peroxisomes, also activated Atg1 using Atg11 with a distinct receptor. Our work reveals that receptor-target complexes activate Atg1 to drive formation of selective autophagosomes. This regulatory logic is a key similarity between selective autophagy and bulk autophagy, which is initiated by a distinct Atg1 activation mechanism during starvation.
authors.affiliation: Northwest Labs, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Roarke A
authors.initials: RA
authors.lastname: Kamber
authors.affiliation: Northwest Labs, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Shoemaker
authors.affiliation: Northwest Labs, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: vdenic@mcb.harvard.edu.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Denic
mesh_terms: D000626:Aminopeptidases / Q000378:metabolism*; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D002474:Cell-Free System; D004789:Enzyme Activation; D066298:In Vitro Techniques; D020675:Peroxisomes / Q000378:metabolism; D010766:Phosphorylation; D066329:Protein Aggregates; D011494:Protein Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C502923:Atg11 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D066329:Protein Aggregates; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D011494:Protein Kinases; C477823:ATG1 protein, S cerevisiae; D000626:Aminopeptidases; C019689:APE1 protein, S cerevisiae