title: Two Independent Pathways within Selective Autophagy Converge to Activate Atg1 Kinase at the Vacuole.
abstract: Autophagy is a potent cellular degradation pathway, and its activation needs to be tightly controlled. Cargo receptors mediate selectivity during autophagy by bringing cargo to the scaffold protein Atg11 and, in turn, to the autophagic machinery, including the central autophagy kinase Atg1. Here we show how selective autophagy is tightly regulated in space and time to prevent aberrant Atg1 kinase activation and autophagy induction. We established an induced bypass approach (iPass) that combines genetic deletion with chemically induced dimerization to evaluate the roles of Atg13 and cargo receptors in Atg1 kinase activation and selective autophagy progression. We show that Atg1 activation does not require cargo receptors, cargo-bound Atg11, or Atg13 per se. Rather, these proteins function in two independent pathways that converge to activate Atg1 at the vacuole. This pathway architecture underlies the spatiotemporal control of Atg1 kinase activity, thereby preventing inappropriate autophagosome formation.
authors: Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030 Vienna, Austria.
authors: Raffaela
authors: R
authors: Torggler
authors: Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030 Vienna, Austria.
authors: Daniel
authors: D
authors: Papinski
authors: Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030 Vienna, Austria.
authors: Thorsten
authors: T
authors: Brach
authors: Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030 Vienna, Austria.
authors: Levent
authors: L
authors: Bas
authors: Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030 Vienna, Austria.
authors: Martina
authors: M
authors: Schuschnig
authors: Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030 Vienna, Austria.
authors: Thaddäus
authors: T
authors: Pfaffenwimmer
authors: Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030 Vienna, Austria.
authors: Sabrina
authors: S
authors: Rohringer
authors: Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030 Vienna, Austria.
authors: Tamara
authors: T
authors: Matzhold
authors: Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030 Vienna, Austria.
authors: David
authors: D
authors: Schweida
authors: Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030 Vienna, Austria.
authors: Andrea
authors: A
authors: Brezovich
authors: Max F. Perutz Laboratories, Vienna Biocenter, University of Vienna, 1030 Vienna, Austria. Electronic address: claudine.kraft@univie.ac.at.
authors: Claudine
authors: C
authors: Kraft
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000235:genetics*; D000071183:Autophagy-Related Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D055503:Protein Multimerization; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014617:Vacuoles / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C413216:ATG13 protein, S cerevisiae; C434480:ATG19 protein, S cerevisiae; D048868:Adaptor Proteins, Signal Transducing; C502923:Atg11 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D049452:Green Fluorescent Proteins; D011494:Protein Kinases; C477823:ATG1 protein, S cerevisiae; D000626:Aminopeptidases; C019689:APE1 protein, S cerevisiae
keywords: Atg1-ULK1 kinase; Atg11; Atg13; Atg19; Atg36; Cvt pathway; autophagy; iPass; pexophagy