Evidence map›Paper›PMID 25079602›Full record

ArticlePLoS genetics2014

Essential genetic interactors of SIR2 required for spatial sequestration and asymmetrical inheritance of protein aggregates.

Jia Song, Qian Yang, Junsheng Yang, Lisa Larsson, Xinxin Hao, Xuefeng Zhu, Sandra Malmgren-Hill, Marija Cvijovic, Julia Fernandez-Rodriguez, Julie Grantham and 3 more

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 90 citations in OpenAlex.

  1. Article
  2. NADCells · 2025
    Review
  3. Article
  4. 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 · 2024
    Article
  5. 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 · 2024
    Article
  6. International journal of molecular sciences · 2023
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Protein aggregation in bacteria.FEMS microbiology reviews · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 2 countries.

Jia SongSchool of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Qian YangSchool of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Junsheng YangDepartment of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
Lisa LarssonDepartment of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
Xinxin HaoDepartment of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
Xuefeng ZhuDepartment of Medical Biochemistry and Cell Biology, University of Gothenburg, Göteborg, Sweden.
Sandra Malmgren-HillDepartment of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
Marija CvijovicMathematical Sciences, University of Gothenburg, Gothenburg, Sweden; Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.
Julia Fernandez-RodriguezCentre for Cellular Imaging, University of Gothenburg, Göteborg, Sweden.
Julie GranthamDepartment of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
Claes M GustafssonDepartment of Medical Biochemistry and Cell Biology, University of Gothenburg, Göteborg, Sweden.
Beidong LiuSchool of Life Science and Technology, Harbin Institute of Technology, Harbin, China; Department of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
Thomas NyströmDepartment of Chemistry and Molecular Biology, University of Gothenburg, Göteborg, Sweden.
University of Gothenburg · SEHarbin Institute of Technology · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Gene Regulatory NetworksActin CytoskeletonActinsCalmodulinCell DivisionCell PolarityEndoplasmic ReticulumGene Expression RegulationHeat-Shock ProteinsMyosin Heavy ChainsMyosin Type VProtein AggregatesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSilent Information Regulator Proteins, Saccharomyces cerevisiaeSirtuin 2ActinsCalmodulinCMD1 protein, S cerevisiaeHeat-Shock ProteinsHsP104 protein, S cerevisiaeHSP42 protein, S cerevisiaeMYO2 protein, S cerevisiaeMyosin Heavy ChainsMyosin Type VProtein AggregatesSaccharomyces cerevisiae ProteinsSilent Information Regulator Proteins, Saccharomyces cerevisiaeSIR2 protein, S cerevisiaeSirtuin 2

Identifiers

PMID25079602
PMCPMC4117435
OpenAlexW1986339417

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.