The yeast guanine nucleotide exchange factor Sec7 is a bottleneck in spatial protein quality control and detoxifies neurological disease proteins.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
28 08 2023
Historique:
received: 30 01 2023
accepted: 23 08 2023
medline: 31 8 2023
pubmed: 29 8 2023
entrez: 28 8 2023
Statut: epublish

Résumé

ER-to-Golgi trafficking partakes in the sorting of misfolded cytoplasmic proteins to reduce their cytological toxicity. We show here that yeast Sec7, a protein involved in proliferation of the Golgi, is part of this pathway and participates in an Hsp70-dependent formation of insoluble protein deposits (IPOD). Sec7 associates with the disaggregase Hsp104 during a mild heat shock and increases the rate of Hsp104 diffusion in an Hsp70-dependent manner when overproduced. Sec7 overproduction increased formation of IPODs from smaller aggregates and mitigated the toxicity of Huntingtin exon-1 upon heat stress while Sec7 depletion increased sensitivity to aẞ42 of the Alzheimer's disease and α-synuclein of the Parkinson's disease, suggesting a role of Sec7 in mitigating proteotoxicity.

Identifiants

pubmed: 37640758
doi: 10.1038/s41598-023-41188-0
pii: 10.1038/s41598-023-41188-0
pmc: PMC10462735
doi:

Substances chimiques

HSP70 Heat-Shock Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

14068

Informations de copyright

© 2023. Springer Nature Limited.

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Auteurs

Roja Babazadeh (R)

Institute for Biomedicine, Sahlgrenska Academy, Centre for Ageing and Health - AgeCap, University of Gothenburg, 405 30, Gothenburg, Sweden.

Kara L Schneider (KL)

Institute for Biomedicine, Sahlgrenska Academy, Centre for Ageing and Health - AgeCap, University of Gothenburg, 405 30, Gothenburg, Sweden.

Arthur Fischbach (A)

Institute for Biomedicine, Sahlgrenska Academy, Centre for Ageing and Health - AgeCap, University of Gothenburg, 405 30, Gothenburg, Sweden.

Xinxin Hao (X)

Institute for Biomedicine, Sahlgrenska Academy, Centre for Ageing and Health - AgeCap, University of Gothenburg, 405 30, Gothenburg, Sweden.

Beidong Liu (B)

Department of Chemistry and Molecular Biology, University of Gothenburg, Medicinaregatan 9 C, 413 90, Gothenburg, Sweden.

Thomas Nystrom (T)

Institute for Biomedicine, Sahlgrenska Academy, Centre for Ageing and Health - AgeCap, University of Gothenburg, 405 30, Gothenburg, Sweden. thomas.nystrom@cmb.gu.se.

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Classifications MeSH