ArticlePLoS genetics2014
Essential genetic interactors of SIR2 required for spatial sequestration and asymmetrical inheritance of protein aggregates.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 90 citations in OpenAlex.
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- Balance between asymmetric allocation and repair of somatic damage in unicellular life forms as an ancient form of r/K selection.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Elimination of virus-like particles reduces protein aggregation and extends replicative lifespan inProceedings of the National Academy of Sciences of the United States of America · 2024Article
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- Unicellular life balances asymmetric allocation and repair of somatic damage representing the origin of r/K selection.bioRxiv : the preprint server for biology · 2023Article
- The yeast guanine nucleotide exchange factor Sec7 is a bottleneck in spatial protein quality control and detoxifies neurological disease proteins.Scientific reports · 2023Article
- Overexpression of Hsp104 by Causing Dissolution of the Prion Seeds Cures the Yeast [International journal of molecular sciences · 2023Article
- Artificial Hsp104-mediated systems for re-localizing protein aggregates.Nature communications · 2023Article
- The cytoprotective sequestration activity of small heat shock proteins is evolutionarily conserved.The Journal of cell biology · 2022Article
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- Lsm7 phase-separated condensates trigger stress granule formation.Nature communications · 2022Article
- Mutant Huntingtin Protein Interaction Map Implicates Dysregulation of Multiple Cellular Pathways in Neurodegeneration of Huntington's Disease.Journal of Huntington's disease · 2022Article
- Differential role of cytosolic Hsp70s in longevity assurance and protein quality control.PLoS genetics · 2021Article
- The actin cytoskeletal network plays a role in yeast prion transmission and contributes to prion stability.Molecular microbiology · 2020Article
- Yeast mismatch repair components are required for stable inheritance of gene silencing.PLoS genetics · 2020Article
- Proteotoxic stress promotes entrapment of ribosomes and misfolded proteins in a shared cytosolic compartment.Nucleic acids research · 2020Article
- Protein aggregation in bacteria.FEMS microbiology reviews · 2020Review
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sir2 is a central regulator of yeast aging and its deficiency increases daughter cell inheritance of stress- and aging-induced misfolded proteins deposited in aggregates and inclusion bodies. Here, by quantifying traits predicted to affect aggregate inheritance in a passive manner, we found that a passive diffusion model cannot explain Sir2-dependent failures in mother-biased segregation of either the small aggregates formed by the misfolded Huntingtin, Htt103Q, disease protein or heat-induced Hsp104-associated aggregates. Instead, we found that the genetic interaction network of SIR2 comprises specific essential genes required for mother-biased segregation including those encoding components of the actin cytoskeleton, the actin-associated myosin V motor protein Myo2, and the actin organization protein calmodulin, Cmd1. Co-staining with Hsp104-GFP demonstrated that misfolded Htt103Q is sequestered into small aggregates, akin to stress foci formed upon heat stress, that fail to coalesce into inclusion bodies. Importantly, these Htt103Q foci, as well as the ATPase-defective Hsp104Y662A-associated structures previously shown to be stable stress foci, co-localized with Cmd1 and Myo2-enriched structures and super-resolution 3-D microscopy demonstrated that they are associated with actin cables. Moreover, we found that Hsp42 is required for formation of heat-induced Hsp104Y662A foci but not Htt103Q foci suggesting that the routes employed for foci formation are not identical. In addition to genes involved in actin-dependent processes, SIR2-interactors required for asymmetrical inheritance of Htt103Q and heat-induced aggregates encode essential sec genes involved in ER-to-Golgi trafficking/ER homeostasis.
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