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

• Published in: Nature communications Vol. 15; no. 1; pp. 2861 - 20
• Main Authors: Coraggio, Francesca, Bhushan, Mahak, Roumeliotis, Spyridon, Caroti, Francesca, Bevilacqua, Carlo, Prevedel, Robert, Rapti, Georgia
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/107; 13/89; 13/95; 14/19; 14/63; 38/22; 38/23; 38/35; 38/39; 38/44; 38/70; 38/77; 38/88; 38/90; 45/22; 49/47; 631/136/1660; 631/378/2596/1308; 631/80/474/1768; 631/80/79/750; 64/11; Aging; Animals; Astrocytes; Biomechanical Phenomena; Biomechanics; Caenorhabditis elegans - genetics; Cell junctions; Disruption; Environmental stress; Extracellular matrix; Extracellular Matrix - metabolism; Functional morphology; Genetics; Glial cells; Hsc70 protein; Hsp70 protein; Humanities and Social Sciences; Hypersensitivity; Integrity; Intercellular Junctions; Material properties; multidisciplinary; Neuroglia; Neuronal-glial interactions; Proteostasis; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-46827-2

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. Neural circuit architecture must be maintained during an animal’s lifetime. Here, the authors show that a protective mechanism combining proteostasis and biomechanics supports the integrity of glial cells to environmental stressors.