Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Abada, Adi, Levin-Zaidman, Smadar, Porat, Ziv, Dadosh, Tali, Elazar, Zvulun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2017
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
_version_ 1783283821971505152
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
work_keys_str_mv AT abadaadi snareprimingisessentialformaturationofautophagosomesbutnotfortheirformation
AT levinzaidmansmadar snareprimingisessentialformaturationofautophagosomesbutnotfortheirformation
AT poratziv snareprimingisessentialformaturationofautophagosomesbutnotfortheirformation
AT dadoshtali snareprimingisessentialformaturationofautophagosomesbutnotfortheirformation
AT elazarzvulun snareprimingisessentialformaturationofautophagosomesbutnotfortheirformation