Trs85 directs a Ypt1 GEF, TRAPPIII, to the phagophore to promote autophagy.
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.
Lynch-Day
Molly A
MA
Departments of Molecular, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA.
Bhandari
Deepali
D
Menon
Shekar
S
Huang
Ju
J
Cai
Huaqing
H
Bartholomew
Clinton R
CR
Brumell
John H
JH
Ferro-Novick
Susan
S
Klionsky
Daniel J
DJ
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*
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