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SNARE priming is essential for maturation of autophagosomes but not for their formation
Autophagy, a unique intracellular membrane-trafficking pathway, is initiated by the formation of an isolation membrane (phagophore) that engulfs cytoplasmic constituents, leading to generation of the autophagosome, a double-membrane vesicle, which is targeted to the lysosome. The outer autophagosoma...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715740/ https://www.ncbi.nlm.nih.gov/pubmed/29138318 http://dx.doi.org/10.1073/pnas.1705572114 |
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author | Abada, Adi Levin-Zaidman, Smadar Porat, Ziv Dadosh, Tali Elazar, Zvulun |
author_facet | Abada, Adi Levin-Zaidman, Smadar Porat, Ziv Dadosh, Tali Elazar, Zvulun |
author_sort | Abada, Adi |
collection | PubMed |
description | Autophagy, a unique intracellular membrane-trafficking pathway, is initiated by the formation of an isolation membrane (phagophore) that engulfs cytoplasmic constituents, leading to generation of the autophagosome, a double-membrane vesicle, which is targeted to the lysosome. The outer autophagosomal membrane consequently fuses with the lysosomal membrane. Multiple membrane-fusion events mediated by SNARE molecules have been postulated to promote autophagy. αSNAP, the adaptor molecule for the SNARE-priming enzyme N-ethylmaleimide-sensitive factor (NSF) is known to be crucial for intracellular membrane fusion processes, but its role in autophagy remains unclear. Here we demonstrated that knockdown of αSNAP leads to inhibition of autophagy, manifested by an accumulation of sealed autophagosomes located in close proximity to lysosomes but not fused with them. Under these conditions, moreover, association of both Atg9 and the autophagy-related SNARE protein syntaxin17 with the autophagosome remained unaffected. Finally, our results suggested that under starvation conditions, the levels of αSNAP, although low, are nevertheless sufficient to partially promote the SNARE priming required for autophagy. Taken together, these findings indicate that while autophagosomal–lysosomal membrane fusion is sensitive to inhibition of SNARE priming, the initial stages of autophagosome biogenesis and autophagosome expansion remain resistant to its loss. |
format | Online Article Text |
id | pubmed-5715740 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-57157402017-12-06 SNARE priming is essential for maturation of autophagosomes but not for their formation Abada, Adi Levin-Zaidman, Smadar Porat, Ziv Dadosh, Tali Elazar, Zvulun Proc Natl Acad Sci U S A Biological Sciences Autophagy, a unique intracellular membrane-trafficking pathway, is initiated by the formation of an isolation membrane (phagophore) that engulfs cytoplasmic constituents, leading to generation of the autophagosome, a double-membrane vesicle, which is targeted to the lysosome. The outer autophagosomal membrane consequently fuses with the lysosomal membrane. Multiple membrane-fusion events mediated by SNARE molecules have been postulated to promote autophagy. αSNAP, the adaptor molecule for the SNARE-priming enzyme N-ethylmaleimide-sensitive factor (NSF) is known to be crucial for intracellular membrane fusion processes, but its role in autophagy remains unclear. Here we demonstrated that knockdown of αSNAP leads to inhibition of autophagy, manifested by an accumulation of sealed autophagosomes located in close proximity to lysosomes but not fused with them. Under these conditions, moreover, association of both Atg9 and the autophagy-related SNARE protein syntaxin17 with the autophagosome remained unaffected. Finally, our results suggested that under starvation conditions, the levels of αSNAP, although low, are nevertheless sufficient to partially promote the SNARE priming required for autophagy. Taken together, these findings indicate that while autophagosomal–lysosomal membrane fusion is sensitive to inhibition of SNARE priming, the initial stages of autophagosome biogenesis and autophagosome expansion remain resistant to its loss. National Academy of Sciences 2017-11-28 2017-11-14 /pmc/articles/PMC5715740/ /pubmed/29138318 http://dx.doi.org/10.1073/pnas.1705572114 Text en Copyright © 2017 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Abada, Adi Levin-Zaidman, Smadar Porat, Ziv Dadosh, Tali Elazar, Zvulun SNARE priming is essential for maturation of autophagosomes but not for their formation |
title | SNARE priming is essential for maturation of autophagosomes but not for their formation |
title_full | SNARE priming is essential for maturation of autophagosomes but not for their formation |
title_fullStr | SNARE priming is essential for maturation of autophagosomes but not for their formation |
title_full_unstemmed | SNARE priming is essential for maturation of autophagosomes but not for their formation |
title_short | SNARE priming is essential for maturation of autophagosomes but not for their formation |
title_sort | snare priming is essential for maturation of autophagosomes but not for their formation |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715740/ https://www.ncbi.nlm.nih.gov/pubmed/29138318 http://dx.doi.org/10.1073/pnas.1705572114 |
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