Journal Article

DZNE-2020-05435

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging.

Lechler, M. C. (First author)DZNE* ; Crawford, E. D.DZNE* ; Groh, N.DZNE* ; Widmaier, K.DZNE* ; Jung, R.DZNE* ; Kirstein, J. ; Trinidad, J. C. ; Burlingame, A. L. ; David, D. (Last author)DZNE*

2017
Elsevier [New York, NY]

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Please use a persistent id in citations: doi:10.1016/j.celrep.2016.12.033

Abstract: 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.

Keyword(s): Aging: metabolism (MeSH) ; Animals (MeSH) ; Caenorhabditis elegans: metabolism (MeSH) ; Caenorhabditis elegans Proteins: metabolism (MeSH) ; Cytoplasmic Granules: metabolism (MeSH) ; Heat-Shock Proteins: metabolism (MeSH) ; Insulin: metabolism (MeSH) ; Insulin-Like Growth Factor I: metabolism (MeSH) ; Longevity (MeSH) ; Mutation: genetics (MeSH) ; Protein Aggregates (MeSH) ; RNA: metabolism (MeSH) ; RNA-Binding Proteins: metabolism (MeSH) ; Receptor, Insulin: metabolism (MeSH) ; Signal Transduction (MeSH) ; Solubility (MeSH) ; Caenorhabditis elegans Proteins ; Heat-Shock Proteins ; Insulin ; Protein Aggregates ; RNA-Binding Proteins ; RNA ; Insulin-Like Growth Factor I ; DAF-2 protein, C elegans ; Receptor, Insulin

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Contributing Institute(s):

1. Protein Aggregation and Aging (AG David)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2017

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Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection

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