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Asymmetric Inheritance of Aggregated Proteins and Age Reset in Yeast Are Regulated by Vac17-Dependent Vacuolar Functions

Age can be reset during mitosis in both yeast and stem cells to generate a young daughter cell from an aged and deteriorated one. This phenomenon requires asymmetry-generating genes (AGGs) that govern the asymmetrical inheritance of aggregated proteins. Using a genome-wide imaging screen to identify...

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Autores principales: Hill, Sandra Malmgren, Hao, Xinxin, Grönvall, Johan, Spikings-Nordby, Stephanie, Widlund, Per O., Amen, Triana, Jörhov, Anna, Josefson, Rebecca, Kaganovich, Daniel, Liu, Beidong, Nyström, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963537/
https://www.ncbi.nlm.nih.gov/pubmed/27373154
http://dx.doi.org/10.1016/j.celrep.2016.06.016
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author Hill, Sandra Malmgren
Hao, Xinxin
Grönvall, Johan
Spikings-Nordby, Stephanie
Widlund, Per O.
Amen, Triana
Jörhov, Anna
Josefson, Rebecca
Kaganovich, Daniel
Liu, Beidong
Nyström, Thomas
author_facet Hill, Sandra Malmgren
Hao, Xinxin
Grönvall, Johan
Spikings-Nordby, Stephanie
Widlund, Per O.
Amen, Triana
Jörhov, Anna
Josefson, Rebecca
Kaganovich, Daniel
Liu, Beidong
Nyström, Thomas
author_sort Hill, Sandra Malmgren
collection PubMed
description Age can be reset during mitosis in both yeast and stem cells to generate a young daughter cell from an aged and deteriorated one. This phenomenon requires asymmetry-generating genes (AGGs) that govern the asymmetrical inheritance of aggregated proteins. Using a genome-wide imaging screen to identify AGGs in Saccharomyces cerevisiae, we discovered a previously unknown role for endocytosis, vacuole fusion, and the myosin-dependent adaptor protein Vac17 in asymmetrical inheritance of misfolded proteins. Overproduction of Vac17 increases deposition of aggregates into cytoprotective vacuole-associated sites, counteracts age-related breakdown of endocytosis and vacuole integrity, and extends replicative lifespan. The link between damage asymmetry and vesicle trafficking can be explained by a direct interaction between aggregates and vesicles. We also show that the protein disaggregase Hsp104 interacts physically with endocytic vesicle-associated proteins, such as the dynamin-like protein, Vps1, which was also shown to be required for Vac17-dependent sequestration of protein aggregates. These data demonstrate that two physiognomies of aging—reduced endocytosis and protein aggregation—are interconnected and regulated by Vac17.
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spelling pubmed-49635372016-08-03 Asymmetric Inheritance of Aggregated Proteins and Age Reset in Yeast Are Regulated by Vac17-Dependent Vacuolar Functions Hill, Sandra Malmgren Hao, Xinxin Grönvall, Johan Spikings-Nordby, Stephanie Widlund, Per O. Amen, Triana Jörhov, Anna Josefson, Rebecca Kaganovich, Daniel Liu, Beidong Nyström, Thomas Cell Rep Article Age can be reset during mitosis in both yeast and stem cells to generate a young daughter cell from an aged and deteriorated one. This phenomenon requires asymmetry-generating genes (AGGs) that govern the asymmetrical inheritance of aggregated proteins. Using a genome-wide imaging screen to identify AGGs in Saccharomyces cerevisiae, we discovered a previously unknown role for endocytosis, vacuole fusion, and the myosin-dependent adaptor protein Vac17 in asymmetrical inheritance of misfolded proteins. Overproduction of Vac17 increases deposition of aggregates into cytoprotective vacuole-associated sites, counteracts age-related breakdown of endocytosis and vacuole integrity, and extends replicative lifespan. The link between damage asymmetry and vesicle trafficking can be explained by a direct interaction between aggregates and vesicles. We also show that the protein disaggregase Hsp104 interacts physically with endocytic vesicle-associated proteins, such as the dynamin-like protein, Vps1, which was also shown to be required for Vac17-dependent sequestration of protein aggregates. These data demonstrate that two physiognomies of aging—reduced endocytosis and protein aggregation—are interconnected and regulated by Vac17. Cell Press 2016-07-19 /pmc/articles/PMC4963537/ /pubmed/27373154 http://dx.doi.org/10.1016/j.celrep.2016.06.016 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Hill, Sandra Malmgren
Hao, Xinxin
Grönvall, Johan
Spikings-Nordby, Stephanie
Widlund, Per O.
Amen, Triana
Jörhov, Anna
Josefson, Rebecca
Kaganovich, Daniel
Liu, Beidong
Nyström, Thomas
Asymmetric Inheritance of Aggregated Proteins and Age Reset in Yeast Are Regulated by Vac17-Dependent Vacuolar Functions
title Asymmetric Inheritance of Aggregated Proteins and Age Reset in Yeast Are Regulated by Vac17-Dependent Vacuolar Functions
title_full Asymmetric Inheritance of Aggregated Proteins and Age Reset in Yeast Are Regulated by Vac17-Dependent Vacuolar Functions
title_fullStr Asymmetric Inheritance of Aggregated Proteins and Age Reset in Yeast Are Regulated by Vac17-Dependent Vacuolar Functions
title_full_unstemmed Asymmetric Inheritance of Aggregated Proteins and Age Reset in Yeast Are Regulated by Vac17-Dependent Vacuolar Functions
title_short Asymmetric Inheritance of Aggregated Proteins and Age Reset in Yeast Are Regulated by Vac17-Dependent Vacuolar Functions
title_sort asymmetric inheritance of aggregated proteins and age reset in yeast are regulated by vac17-dependent vacuolar functions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963537/
https://www.ncbi.nlm.nih.gov/pubmed/27373154
http://dx.doi.org/10.1016/j.celrep.2016.06.016
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