Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging
| Autor: | Janine Kirstein, Katja Widmaier, Jonathan C. Trinidad, Marie C. Lechler, Emily D. Crawford, Della C. David, Nicole Groh, Alma L. Burlingame, Raimund Jung |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
metabolism [Caenorhabditis elegans Proteins] Aging medicine.medical_treatment RNA-binding protein Protein aggregation Insulin neurodegenerative diseases longevity protein aggregation HSF-1 RNA-binding proteins DAF-2 Caenorhabditis elegans aging stress granules Insulin-Like Growth Factor I metabolism [Insulin-Like Growth Factor I] lcsh:QH301-705.5 Heat-Shock Proteins DAF-2 protein C elegans Neurodegeneration RNA-Binding Proteins metabolism [Caenorhabditis elegans] Cell biology metabolism [RNA] Daf-2 Signal Transduction endocrine system Longevity genetics [Mutation] Biology Cytoplasmic Granules metabolism [RNA-Binding Proteins] General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Protein Aggregates Stress granule medicine Animals ddc:610 metabolism [Aging] Caenorhabditis elegans Proteins Growth factor RNA medicine.disease metabolism [Cytoplasmic Granules] Receptor Insulin Heat shock factor metabolism [Insulin] 030104 developmental biology lcsh:Biology (General) Solubility Mutation metabolism [Heat-Shock Proteins] metabolism [Receptor Insulin] |
| Zdroj: | Cell reports 18(2), 454-467 (2017). doi:10.1016/j.celrep.2016.12.033 Cell Reports Cell reports, 18(2): 454–467 Cell Reports, Vol 18, Iss 2, Pp 454-467 (2017) |
| Popis: | Summary Low-complexity “prion-like” domains in key RNA-binding proteins (RBPs) mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components, including stress granule proteins, become highly insoluble with age in C. elegans and that reduced insulin/insulin-like growth factor 1 (IGF-1) daf-2 receptor signaling efficiently prevents their aggregation. Importantly, stress-granule-related RBP aggregates are associated with reduced fitness. We show that heat shock transcription factor 1 (HSF-1) is a main regulator of stress-granule-related RBP aggregation in both young and aged animals. During aging, increasing DAF-16 activity restores dynamic stress-granule-related RBPs, partly by decreasing the buildup of other misfolded proteins that seed RBP aggregation. Longevity-associated mechanisms found to maintain dynamic RBPs during aging could be relevant for neurodegenerative diseases. Graphical Abstract Highlights • RNA-binding proteins (RBPs) with “prion-like” domains form solid aggregates with age • Reduced daf-2 signaling preferentially prevents insolubility of RNA granule proteins • Co-aggregation with other misfolded proteins promotes stress granule RBP aggregation • Aggregation of key stress-granule-related RBPs is associated with impaired health Lechler et al. show that RNA-binding proteins (RBPs) including stress granule proteins are prone to aggregate with age in C. elegans. Aggregation of stress granule RBPs with “prion-like” domains is associated with reduced fitness. Their aggregation is prevented by longevity pathways and promoted by the aggregation of other misfolded proteins. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|