title: Trs85 directs a Ypt1 GEF, TRAPPIII, to the phagophore to promote autophagy.
abstract: Macroautophagy (hereafter autophagy) is a ubiquitous process in eukaryotic cells that is integrally involved in various aspects of cellular and organismal physiology. The morphological hallmark of autophagy is the formation of double-membrane cytosolic vesicles, autophagosomes, which sequester cytoplasmic cargo and deliver it to the lysosome or vacuole. Thus, autophagy involves dynamic membrane mobilization, yet the source of the lipid that forms the autophagosomes and the mechanism of membrane delivery are poorly characterized. The TRAPP complexes are multimeric guanine nucleotide exchange factors (GEFs) that activate the Rab GTPase Ypt1, which is required for secretion. Here we describe another form of this complex (TRAPPIII) that acts as an autophagy-specific GEF for Ypt1. The Trs85 subunit of the TRAPPIII complex directs this Ypt1 GEF to the phagophore assembly site (PAS) that is involved in autophagosome formation. Consistent with the observation that a Ypt1 GEF is directed to the PAS, we find that Ypt1 is essential for autophagy. This is an example of a Rab GEF that is specifically targeted for canonical autophagosome formation.
authors.affiliation: Departments of Molecular, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA.
authors.forename: Molly A
authors.initials: MA
authors.lastname: Lynch-Day
authors.forename: Deepali
authors.initials: D
authors.lastname: Bhandari
authors.forename: Shekar
authors.initials: S
authors.lastname: Menon
authors.forename: Ju
authors.initials: J
authors.lastname: Huang
authors.forename: Huaqing
authors.initials: H
authors.lastname: Cai
authors.forename: Clinton R
authors.initials: CR
authors.lastname: Bartholomew
authors.forename: John H
authors.initials: JH
authors.lastname: Brumell
authors.forename: Susan
authors.initials: S
authors.lastname: Ferro-Novick
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Klionsky
mesh_terms: D001343:Autophagy / Q000502:physiology*; D002850:Chromatography, Gel; D017931:DNA Primers / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D015151:Immunoblotting; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D010588:Phagosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D020662:Guanine Nucleotide Exchange Factors; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C406327:transport protein particle, TRAPP; C060755:YPT1 protein, S cerevisiae; D020691:rab GTP-Binding Proteins