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Function of the SNARE Ykt6 on autophagosomes requires the Dsl1 complex and the Atg1 kinase complex

The mechanism and regulation of fusion between autophagosomes and lysosomes/vacuoles are still only partially understood in both yeast and mammals. In yeast, this fusion step requires SNARE proteins, the homotypic vacuole fusion and protein sorting (HOPS) tethering complex, the RAB7 GTPase Ypt7, and...

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Autores principales: Gao, Jieqiong, Kurre, Rainer, Rose, Jaqueline, Walter, Stefan, Fröhlich, Florian, Piehler, Jacob, Reggiori, Fulvio, Ungermann, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726795/
https://www.ncbi.nlm.nih.gov/pubmed/33025734
http://dx.doi.org/10.15252/embr.202050733
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author Gao, Jieqiong
Kurre, Rainer
Rose, Jaqueline
Walter, Stefan
Fröhlich, Florian
Piehler, Jacob
Reggiori, Fulvio
Ungermann, Christian
author_facet Gao, Jieqiong
Kurre, Rainer
Rose, Jaqueline
Walter, Stefan
Fröhlich, Florian
Piehler, Jacob
Reggiori, Fulvio
Ungermann, Christian
author_sort Gao, Jieqiong
collection PubMed
description The mechanism and regulation of fusion between autophagosomes and lysosomes/vacuoles are still only partially understood in both yeast and mammals. In yeast, this fusion step requires SNARE proteins, the homotypic vacuole fusion and protein sorting (HOPS) tethering complex, the RAB7 GTPase Ypt7, and its guanine nucleotide exchange factor (GEF) Mon1‐Ccz1. We and others recently identified Ykt6 as the autophagosomal SNARE protein. However, it has not been resolved when and how lipid‐anchored Ykt6 is recruited onto autophagosomes. Here, we show that Ykt6 is recruited at an early stage of the formation of these carriers through a mechanism that depends on endoplasmic reticulum (ER)‐resident Dsl1 complex and COPII‐coated vesicles. Importantly, Ykt6 activity on autophagosomes is regulated by the Atg1 kinase complex, which inhibits Ykt6 through direct phosphorylation. Thus, our findings indicate that the Ykt6 pool on autophagosomal membranes is kept inactive by Atg1 phosphorylation, and once an autophagosome is ready to fuse with vacuole, Ykt6 dephosphorylation allows its engagement in the fusion event.
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spelling pubmed-77267952020-12-13 Function of the SNARE Ykt6 on autophagosomes requires the Dsl1 complex and the Atg1 kinase complex Gao, Jieqiong Kurre, Rainer Rose, Jaqueline Walter, Stefan Fröhlich, Florian Piehler, Jacob Reggiori, Fulvio Ungermann, Christian EMBO Rep Articles The mechanism and regulation of fusion between autophagosomes and lysosomes/vacuoles are still only partially understood in both yeast and mammals. In yeast, this fusion step requires SNARE proteins, the homotypic vacuole fusion and protein sorting (HOPS) tethering complex, the RAB7 GTPase Ypt7, and its guanine nucleotide exchange factor (GEF) Mon1‐Ccz1. We and others recently identified Ykt6 as the autophagosomal SNARE protein. However, it has not been resolved when and how lipid‐anchored Ykt6 is recruited onto autophagosomes. Here, we show that Ykt6 is recruited at an early stage of the formation of these carriers through a mechanism that depends on endoplasmic reticulum (ER)‐resident Dsl1 complex and COPII‐coated vesicles. Importantly, Ykt6 activity on autophagosomes is regulated by the Atg1 kinase complex, which inhibits Ykt6 through direct phosphorylation. Thus, our findings indicate that the Ykt6 pool on autophagosomal membranes is kept inactive by Atg1 phosphorylation, and once an autophagosome is ready to fuse with vacuole, Ykt6 dephosphorylation allows its engagement in the fusion event. John Wiley and Sons Inc. 2020-10-07 2020-12-03 /pmc/articles/PMC7726795/ /pubmed/33025734 http://dx.doi.org/10.15252/embr.202050733 Text en © 2020 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Gao, Jieqiong
Kurre, Rainer
Rose, Jaqueline
Walter, Stefan
Fröhlich, Florian
Piehler, Jacob
Reggiori, Fulvio
Ungermann, Christian
Function of the SNARE Ykt6 on autophagosomes requires the Dsl1 complex and the Atg1 kinase complex
title Function of the SNARE Ykt6 on autophagosomes requires the Dsl1 complex and the Atg1 kinase complex
title_full Function of the SNARE Ykt6 on autophagosomes requires the Dsl1 complex and the Atg1 kinase complex
title_fullStr Function of the SNARE Ykt6 on autophagosomes requires the Dsl1 complex and the Atg1 kinase complex
title_full_unstemmed Function of the SNARE Ykt6 on autophagosomes requires the Dsl1 complex and the Atg1 kinase complex
title_short Function of the SNARE Ykt6 on autophagosomes requires the Dsl1 complex and the Atg1 kinase complex
title_sort function of the snare ykt6 on autophagosomes requires the dsl1 complex and the atg1 kinase complex
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726795/
https://www.ncbi.nlm.nih.gov/pubmed/33025734
http://dx.doi.org/10.15252/embr.202050733
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