SNARE Proteins Are Required for Macroautophagy

Macroautophagy mediates the degradation of long-lived proteins and organelles via the de novo formation of double-membrane autophagosomes that sequester cytoplasm and deliver it to the vacuole/lysosome; however, relatively little is known about autophagosome biogenesis. Atg8, a phosphatidylethanolam...

Full description

Saved in:
Bibliographic Details
Published in:Cell 2011-07, Vol.146 (2), p.290-302
Main Authors: Nair, Usha, Jotwani, Anjali, Geng, Jiefei, Gammoh, Noor, Richerson, Diana, Yen, Wei-Lien, Griffith, Janice, Nag, Shanta, Wang, Ke, Moss, Tyler, Baba, Misuzu, McNew, James A., Jiang, Xuejun, Reggiori, Fulvio, Melia, Thomas J., Klionsky, Daniel J.
Format: Article
Language:English
Subjects:
Autophagy
Autophagy-Related Protein 8 Family
Autophagy-Related Proteins
biogenesis
Liposomes - metabolism
lysosomes
Membrane Proteins - metabolism
Microtubule-Associated Proteins - metabolism
Phagosomes - metabolism
phosphatidylethanolamines
Phosphatidylethanolamines - metabolism
proteins
Qa-SNARE Proteins - metabolism
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - metabolism
SNARE Proteins - metabolism
vacuoles
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Macroautophagy mediates the degradation of long-lived proteins and organelles via the de novo formation of double-membrane autophagosomes that sequester cytoplasm and deliver it to the vacuole/lysosome; however, relatively little is known about autophagosome biogenesis. Atg8, a phosphatidylethanolamine-conjugated protein, was previously proposed to function in autophagosome membrane expansion, based on the observation that it mediates liposome tethering and hemifusion in vitro. We show here that with physiological concentrations of phosphatidylethanolamine, Atg8 does not act as a fusogen. Rather, we provide evidence for the involvement of exocytic Q/t-SNAREs in autophagosome formation, acting in the recruitment of key autophagy components to the site of autophagosome formation, and in regulating the organization of Atg9 into tubulovesicular clusters. Additionally, we found that the endosomal Q/t-SNARE Tlg2 and the R/v-SNAREs Sec22 and Ykt6 interact with Sso1-Sec9, and are required for normal Atg9 transport. Thus, multiple SNARE-mediated fusion events are likely to be involved in autophagosome biogenesis. [Display omitted] ► Biogenesis of the phagophore (autophagosome precursor) requires SNAREs ► At physiological levels, Atg8 does not drive autophagosome membrane hemifusion ► Sso1/2 SNAREs mediate the tubulovesicular organization of Atg9-containing vesicles ► SNAREs Sec22, Tlg2, and Ykt6 complex with Sso1-Sec9 for autophagosome biogenesis
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2011.06.022