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 cytop...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 107; no. 17; pp. 7811 - 7816
Main Authors Lynch-Day, Molly A, Bhandari, Deepali, Menon, Shekar, Huang, Ju, Cai, Huaqing, Bartholomew, Clinton R, Brumell, John H, Ferro-Novick, Susan, Klionsky, Daniel J
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 27.04.2010
National Acad Sciences
Subjects
Antibodies
Autophagy
Autophagy - physiology
Biological Sciences
Biological transport
Chromatography, Gel
Cytoplasm
DNA Primers - genetics
Eukaryotes
Fluorescence
Guanine Nucleotide Exchange Factors - metabolism
Immunoblotting
Immunoprecipitation
Lipids
Membranes
Microscopy, Fluorescence
P branes
Phagosomes - metabolism
rab GTP-Binding Proteins - metabolism
Saccharomyces cerevisiae - physiology
Saccharomyces cerevisiae Proteins - metabolism
Secretory pathway
Starvation
Traffic
Vacuoles
Vesicular Transport Proteins - metabolism
Yeasts
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Summary: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.
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Author contributions: M.A.L.-D., D.B., S.M., J.H., H.C., C.R.B., J.H.B., S.F.-N., and D.J.K. designed research; M.A.L.-D., D.B., S.M., J.H., H.C., and C.R.B. performed research; M.A.L.-D., D.B., H.C., and C.R.B. contributed new reagents/analytic tools; M.A.L.-D., D.B., S.M., J.H., H.C., C.R.B., J.H.B., S.F.-N., and D.J.K. analyzed data; and M.A.L.-D., D.B., J.H., S.F.-N., and D.J.K. wrote the paper.
1M.A.L.-D. and D.B. contributed equally to this work.
Edited* by William T. Wickner, Dartmouth Medical School, Hanover, NH, and approved March 11, 2010 (received for review January 6, 2010)
2Present address: Department of Cell Biology, The Johns Hopkins School of Medicine, Baltimore, MD 21205.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1000063107