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Age-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture

Tissue integrity is sensitive to temperature, tension, age, and is sustained throughout life by adaptive cell-autonomous or extrinsic mechanisms. Safeguarding the remarkably-complex architectures of neurons and glia ensures age-dependent integrity of functional circuits. Here, we report mechanisms s...

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Main Authors: Coraggio, Francesca (Author) , Bhushan, Mahak (Author) , Roumeliotis, Spyridon (Author) , Caroti, Francesca (Author) , Bevilacqua, Carlo (Author) , Prevedel, Robert (Author) , Rapti, Georgia (Author)
Format: Article (Journal)
Language:English
Published: 2024
In: Nature Communications
Year: 2024, Volume: 15, Pages: 1-20
ISSN:2041-1723
DOI:10.1038/s41467-024-46827-2
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-024-46827-2
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-024-46827-2
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Author Notes:Francesca Coraggio, Mahak Bhushan, Spyridon Roumeliotis, Francesca Caroti, Carlo Bevilacqua, Robert Prevedel & Georgia Rapti
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Summary:Tissue integrity is sensitive to temperature, tension, age, and is sustained throughout life by adaptive cell-autonomous or extrinsic mechanisms. Safeguarding the remarkably-complex architectures of neurons and glia ensures age-dependent integrity of functional circuits. Here, we report mechanisms sustaining the integrity of C. elegans CEPsh astrocyte-like glia. We combine large-scale genetics with manipulation of genes, cells, and their environment, quantitative imaging of cellular/ subcellular features, tissue material properties and extracellular matrix (ECM). We identify mutants with age-progressive, environment-dependent defects in glial architecture, consequent disruption of neuronal architecture, and abnormal aging. Functional loss of epithelial Hsp70/Hsc70-cochaperone BAG2 causes ECM disruption, altered tissue biomechanics, and hypersensitivity of glia to environmental temperature and mechanics. Glial-cell junctions ensure epithelia-ECM-CEPsh glia association. Modifying glial junctions or ECM mechanics safeguards glial integrity against disrupted BAG2-proteostasis. Overall, we present a finely-regulated interplay of proteostasis-ECM and cell junctions with conserved components that ensures age-progressive robustness of glial architecture.
Item Description:Online veröffentlicht: 3. April 2024
Gesehen am 06.09.2024
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-024-46827-2

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