Cargo binding to Atg19 unmasks additional Atg8 binding sites to mediate membrane-cargo apposition during selective autophagy.
Autophagy protects cells from harmful substances such as protein aggregates, damaged mitochondria and intracellular pathogens, and has been implicated in a variety of diseases. Selectivity of autophagic processes is mediated by cargo receptors that link cargo to Atg8 family proteins on the developing autophagosomal membrane. To avoid collateral degradation during constitutive autophagic pathways, the autophagic machinery must not only select cargo but also exclude non-cargo material. Here we show that cargo directly activates the cargo receptor Atg19 by exposing multiple Atg8 binding sites. Furthermore, Atg19 mediates tight apposition of the cargo and Atg8-coated membranes in a fully reconstituted system. These properties are essential for the function of Atg19 during selective autophagy in vivo. Our results suggest that cargo receptors contribute to tight membrane bending of the isolation membrane around the cargo.
Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.
Justyna
J
Sawa-Makarska
Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.
Christine
C
Abert
Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.
Julia
J
Romanov
Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.
Bettina
B
Zens
Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.
Iosune
I
Ibiricu
Max F. Perutz Laboratories, University of Vienna, Vienna Biocenter, Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.
Sascha
S
Martens
D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010714:Phosphatidylethanolamines / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D053835:Unilamellar Liposomes / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
C434480:ATG19 protein, S cerevisiae; C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D008164:Luminescent Proteins; D008869:Microtubule-Associated Proteins; D010714:Phosphatidylethanolamines; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D053835:Unilamellar Liposomes; D033921:Vesicular Transport Proteins; C483858:phosphatidylethanolamine