Age-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture
Abstract 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 mec...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46827-2 |
| _version_ | 1797219727648489472 |
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| author | Francesca Coraggio Mahak Bhushan Spyridon Roumeliotis Francesca Caroti Carlo Bevilacqua Robert Prevedel Georgia Rapti |
| author_facet | Francesca Coraggio Mahak Bhushan Spyridon Roumeliotis Francesca Caroti Carlo Bevilacqua Robert Prevedel Georgia Rapti |
| author_sort | Francesca Coraggio |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-24T12:38:15Z |
| format | Article |
| id | doaj.art-49e382ad403d42fdab6ca7e519e3d5b0 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T12:38:15Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-49e382ad403d42fdab6ca7e519e3d5b02024-04-07T11:23:26ZengNature PortfolioNature Communications2041-17232024-04-0115112010.1038/s41467-024-46827-2Age-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architectureFrancesca Coraggio0Mahak Bhushan1Spyridon Roumeliotis2Francesca Caroti3Carlo Bevilacqua4Robert Prevedel5Georgia Rapti6Developmental Biology Unit, European Molecular Biology LaboratoryDevelopmental Biology Unit, European Molecular Biology LaboratoryDevelopmental Biology Unit, European Molecular Biology LaboratoryDevelopmental Biology Unit, European Molecular Biology LaboratoryCell Biology and Biophysics Unit, European Molecular Biology LaboratoryDevelopmental Biology Unit, European Molecular Biology LaboratoryDevelopmental Biology Unit, European Molecular Biology LaboratoryAbstract 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.https://doi.org/10.1038/s41467-024-46827-2 |
| spellingShingle | Francesca Coraggio Mahak Bhushan Spyridon Roumeliotis Francesca Caroti Carlo Bevilacqua Robert Prevedel Georgia Rapti Age-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture Nature Communications |
| title | Age-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture |
| title_full | Age-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture |
| title_fullStr | Age-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture |
| title_full_unstemmed | Age-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture |
| title_short | Age-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture |
| title_sort | age progressive interplay of hsp proteostasis ecm cell junctions and biomechanics ensures c elegans astroglial architecture |
| url | https://doi.org/10.1038/s41467-024-46827-2 |
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