title: TRAPPIII is responsible for vesicular transport from early endosomes to Golgi, facilitating Atg9 cycling in autophagy.
abstract: Autophagy is a bulk protein-degradation process that is regulated by many factors. In this study, we quantitatively assessed the contribution of each essential yeast gene to autophagy. Of the contributing factors that we identified, we focused on the TRAPPIII complex, which was recently shown to act as a guanine-nucleotide exchange factor for the Rab small GTPase Ypt1. Autophagy is defective in the TRAPPIII mutant under nutrient-rich conditions (Cvt pathway), but starvation-induced autophagy is only partially affected. Here, we show that TRAPPIII functions at the Golgi complex to receive general retrograde vesicle traffic from early endosomes. Cargo proteins in this TRAPPIII-dependent pathway include Atg9, a transmembrane protein that is essential for autophagy, and Snc1, a SNARE unrelated to autophagy. When cells were starved, further disruption of vesicle movement from late endosomes to the Golgi caused defects in Atg9 trafficking and autophagy. Thus, TRAPPIII-dependent sorting pathways provide Atg9 reservoirs for pre-autophagosomal structure and phagophore assembly sites under nutrient-rich conditions, whereas the late endosome-to-Golgi pathway is added to these reservoirs when nutrients are limited. This clarification of the role of TRAPPIII elucidates how general membrane traffic contributes to autophagy.
authors.affiliation: Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Osaka University, 565-0871 Osaka, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Shirahama-Noda
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kira
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yoshimori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Noda
mesh_terms: D001343:Autophagy; D000071183:Autophagy-Related Proteins; D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C434065:ATG9 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; C579080:TRS85 protein, S cerevisiae; D033921:Vesicular Transport Proteins
keywords: Atg9; Autophagy; Golgi-associated retrograde protein; Retromer; Snc1; Sorting nexin; TRAPP