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Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17

Macroautophagy is an evolutionarily conserved catabolic mechanism that delivers intracellular constituents to lysosomes using autophagosomes. To achieve degradation, lysosomes must fuse with closed autophagosomes. We previously reported that the soluble N-ethylmaleimide–sensitive factor attachment p...

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Detalles Bibliográficos
Autores principales: Matsui, Takahide, Jiang, Peidu, Nakano, Saori, Sakamaki, Yuriko, Yamamoto, Hayashi, Mizushima, Noboru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080929/
https://www.ncbi.nlm.nih.gov/pubmed/29789439
http://dx.doi.org/10.1083/jcb.201712058
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author Matsui, Takahide
Jiang, Peidu
Nakano, Saori
Sakamaki, Yuriko
Yamamoto, Hayashi
Mizushima, Noboru
author_facet Matsui, Takahide
Jiang, Peidu
Nakano, Saori
Sakamaki, Yuriko
Yamamoto, Hayashi
Mizushima, Noboru
author_sort Matsui, Takahide
collection PubMed
description Macroautophagy is an evolutionarily conserved catabolic mechanism that delivers intracellular constituents to lysosomes using autophagosomes. To achieve degradation, lysosomes must fuse with closed autophagosomes. We previously reported that the soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) protein syntaxin (STX) 17 translocates to autophagosomes to mediate fusion with lysosomes. In this study, we report an additional mechanism. We found that autophagosome–lysosome fusion is retained to some extent even in STX17 knockout (KO) HeLa cells. By screening other human SNAREs, we identified YKT6 as a novel autophagosomal SNARE protein. Depletion of YKT6 inhibited autophagosome–lysosome fusion partially in wild-type and completely in STX17 KO cells, suggesting that YKT6 and STX17 are independently required for fusion. YKT6 formed a SNARE complex with SNAP29 and lysosomal STX7, both of which are required for autophagosomal fusion. Recruitment of YKT6 to autophagosomes depends on its N-terminal longin domain but not on the C-terminal palmitoylation and farnesylation that are essential for its Golgi localization. These findings suggest that two independent SNARE complexes mediate autophagosome–lysosome fusion.
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spelling pubmed-60809292019-02-06 Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17 Matsui, Takahide Jiang, Peidu Nakano, Saori Sakamaki, Yuriko Yamamoto, Hayashi Mizushima, Noboru J Cell Biol Research Articles Macroautophagy is an evolutionarily conserved catabolic mechanism that delivers intracellular constituents to lysosomes using autophagosomes. To achieve degradation, lysosomes must fuse with closed autophagosomes. We previously reported that the soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) protein syntaxin (STX) 17 translocates to autophagosomes to mediate fusion with lysosomes. In this study, we report an additional mechanism. We found that autophagosome–lysosome fusion is retained to some extent even in STX17 knockout (KO) HeLa cells. By screening other human SNAREs, we identified YKT6 as a novel autophagosomal SNARE protein. Depletion of YKT6 inhibited autophagosome–lysosome fusion partially in wild-type and completely in STX17 KO cells, suggesting that YKT6 and STX17 are independently required for fusion. YKT6 formed a SNARE complex with SNAP29 and lysosomal STX7, both of which are required for autophagosomal fusion. Recruitment of YKT6 to autophagosomes depends on its N-terminal longin domain but not on the C-terminal palmitoylation and farnesylation that are essential for its Golgi localization. These findings suggest that two independent SNARE complexes mediate autophagosome–lysosome fusion. Rockefeller University Press 2018-08-06 /pmc/articles/PMC6080929/ /pubmed/29789439 http://dx.doi.org/10.1083/jcb.201712058 Text en © 2018 Matsui et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Matsui, Takahide
Jiang, Peidu
Nakano, Saori
Sakamaki, Yuriko
Yamamoto, Hayashi
Mizushima, Noboru
Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17
title Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17
title_full Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17
title_fullStr Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17
title_full_unstemmed Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17
title_short Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17
title_sort autophagosomal ykt6 is required for fusion with lysosomes independently of syntaxin 17
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080929/
https://www.ncbi.nlm.nih.gov/pubmed/29789439
http://dx.doi.org/10.1083/jcb.201712058
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