title: Ypt1 recruits the Atg1 kinase to the preautophagosomal structure.
abstract: When macroautophagy, a catabolic process that rids the cells of unwanted proteins, is initiated, 30-60 nm Atg9 vesicles move from the Golgi to the preautophagosomal structure (PAS) to initiate autophagosome formation. The Rab GTPase Ypt1 and its mammalian homolog Rab1 regulate macroautophagy and two other trafficking events: endoplasmic reticulum-Golgi and intra-Golgi traffic. How a Rab, which localizes to three distinct cellular locations, achieves specificity is unknown. Here we show that transport protein particle III (TRAPPIII), a conserved autophagy-specific guanine nucleotide exchange factor for Ypt1/Rab1, is recruited to the PAS by Atg17. We also show that activated Ypt1 recruits the putative membrane curvature sensor Atg1 to the PAS, bringing it into proximity to its binding partner Atg17. Since Atg17 resides at the PAS, these events ensure that Atg1 will specifically localize to the PAS and not to the other compartments where Ypt1 resides. We propose that Ypt1 regulates Atg9 vesicle tethering by modulating the delivery of Atg1 to the PAS. These events appear to be conserved in higher cells.
authors.affiliation: Department of Cellular and Molecular Medicine and Howard Hughes Medical Institute, University of California at San Diego, La Jolla, CA 92093-0668, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Shekar
authors.initials: S
authors.lastname: Menon
authors.forename: Akinori
authors.initials: A
authors.lastname: Yamasaki
authors.forename: Hui-Ting
authors.initials: HT
authors.lastname: Chou
authors.forename: Thomas
authors.initials: T
authors.lastname: Walz
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.forename: Susan
authors.initials: S
authors.lastname: Ferro-Novick
mesh_terms: D000818:Animals; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog; D000071183:Autophagy-Related Proteins; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D006056:Golgi Apparatus / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D010588:Phagosomes / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020761:rab1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C434065:ATG9 protein, S cerevisiae; C505602:Atg17 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C406327:transport protein particle, TRAPP; D049452:Green Fluorescent Proteins; D011494:Protein Kinases; C477823:ATG1 protein, S cerevisiae; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C484754:ULK1 protein, human; C060755:YPT1 protein, S cerevisiae; D020691:rab GTP-Binding Proteins; D020761:rab1 GTP-Binding Proteins
keywords: GEF; membrane tethering