An interplay of HSP-proteostasis, biomechanics and ECM-cell junctions 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, functional circuit integrity. Here we report mechanisms sustaining integrity of the C. elegans astrocyte-like CEPsh glia. We combine large-scale genetics with manipulation of genes, cells, and their environment, with quantitative imaging of cellular, subcellular features and material properties of tissues and extracellular matrix (ECM). We identify mutants with age-progressive, environment-dependent defects in glial architecture, consequent disruption of axons, synapses, and aging. Functional loss of epithelial Hsp70/Hsc70-cochaperone BAG2 causes ECM disruption, altered animal biomechanics, and hypersensitivity of glial cells to environmental temperature and mechanics. Glial-cell junctions ensure ECM-CEPsh glia-epithelia 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-progressively the robustness of glial architecture.