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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2016
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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. |
format | Online Article Text |
id | pubmed-4963537 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
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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