SNARE proteins are required for macroautophagy

Usha Nair, Anjali Jotwani, Jiefei Geng, Noor Gammoh, Diana Richerson, Wei-Lien Yen, Janice Griffith, Shanta Nag, Ke Wang, Tyler Moss, Misuzu Baba, James A McNew, Xuejun Jiang, Fulvio Reggiori, Thomas J Melia, Daniel J Klionsky

OnderzoeksoutputAcademicpeer review

340 Citaten (Scopus)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)290-302
Aantal pagina's13
TijdschriftCell
Volume146
Nummer van het tijdschrift2
DOI's
StatusPublished - 22-jul.-2011
Extern gepubliceerdJa

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