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

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Hill, Sandra Malmgren,1987Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institutionen för kemi och molekylärbiologi,Institute of Biomedicine,Department of Chemistry and Molecular Biology (author)

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

Article/chapterEnglish2016

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Elsevier BV,2016

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LIBRIS-ID:oai:gup.ub.gu.se/242393
https://gup.ub.gu.se/publication/242393URI
https://doi.org/10.1016/j.celrep.2016.06.016DOI

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Language:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
life-span
saccharomyces-cerevisiae
damaged proteins
misfolded
proteins
actin cytoskeleton
quality-control
budding yeast
v-atpase
fusion
chaperone
Cell Biology

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Hao, XinxinGothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Institutionen för biomedicin,Department of Chemistry and Molecular Biology,Institute of Biomedicine(Swepub:gu)xxinha (author)
Grönvall, JohanGothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology (author)
Spikings-Nordby, StephanieGothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology (author)
Widlund, Per OGothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institutionen för kemi och molekylärbiologi,Institute of Biomedicine,Department of Chemistry and Molecular Biology(Swepub:gu)xwidlp (author)
Amen, T. (author)
Jorhov, AnnaGothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology (author)
Josefson, RebeccaGothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institutionen för kemi och molekylärbiologi,Institute of Biomedicine,Department of Chemistry and Molecular Biology(Swepub:gu)xlinre (author)
Kaganovich, D. (author)
Liu, Beidong,1972Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology(Swepub:gu)xbeili (author)
Nyström, Thomas,1960Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institutionen för kemi och molekylärbiologi,Institute of Biomedicine,Department of Chemistry and Molecular Biology(Swepub:gu)xnysth (author)
Göteborgs universitetInstitutionen för biomedicin (creator_code:org_t)

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In:Cell Reports: Elsevier BV16:3, s. 826-8382211-1247

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By the author/editor: Hill, Sandra Mal ...; Hao, Xinxin; Grönvall, Johan; Spikings-Nordby, ...; Widlund, Per O; Amen, T.; show more...; Jorhov, Anna; Josefson, Rebecc ...; Kaganovich, D.; Liu, Beidong, 19 ...; Nyström, Thomas, ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

Articles in the publication: Cell Reports

By the university: University of Gothenburg

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