Extracellular proteostasis prevents aggregation during pathogenic attack
| Autor: | Raimund Jung, Waltraud Röseler, Sinem Agilkaya, Ivan Gallotta, Martin Haslbeck, Ralf J. Sommer, Della C. David, Christian Rödelsperger, Chaolie Huang, Jane L. Blersch, Aneet Sandhu, Maximilian Peters |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
metabolism [Caenorhabditis elegans Proteins]
Aging Proteome metabolism [Fatty Acid-Binding Proteins] MAP Kinase Signaling System Protein aggregation Fatty Acid-Binding Proteins Protein Aggregation Pathological prevention & control [Protein Aggregation Pathological] 03 medical and health sciences Protein Aggregates 0302 clinical medicine cytology [Caenorhabditis elegans] RNA interference microbiology [Caenorhabditis elegans] Extracellular metabolism [Extracellular Space] Animals ddc:530 metabolism [Aging] Caenorhabditis elegans Caenorhabditis elegans Proteins 030304 developmental biology 0303 health sciences Multidisciplinary biology Chemistry metabolism [Caenorhabditis elegans] metabolism [Proteome] biology.organism_classification Cell biology Proteostasis Proteotoxicity genetics [Proteome] genetics [Caenorhabditis elegans] RNA Interference Extracellular Space 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Nature |
| Popis: | In metazoans, the secreted proteome participates in intercellular signalling and innate immunity, and builds the extracellular matrix scaffold around cells. Compared with the relatively constant intracellular environment, conditions for proteins in the extracellular space are harsher, and low concentrations of ATP prevent the activity of intracellular components of the protein quality-control machinery. Until now, only a few bona fide extracellular chaperones and proteases have been shown to limit the aggregation of extracellular proteins1–5. Here we performed a systematic analysis of the extracellular proteostasis network in Caenorhabditis elegans with an RNA interference screen that targets genes that encode the secreted proteome. We discovered 57 regulators of extracellular protein aggregation, including several proteins related to innate immunity. Because intracellular proteostasis is upregulated in response to pathogens6–9, we investigated whether pathogens also stimulate extracellular proteostasis. Using a pore-forming toxin to mimic a pathogenic attack, we found that C. elegans responded by increasing the expression of components of extracellular proteostasis and by limiting aggregation of extracellular proteins. The activation of extracellular proteostasis was dependent on stress-activated MAP kinase signalling. Notably, the overexpression of components of extracellular proteostasis delayed ageing and rendered worms resistant to intoxication. We propose that enhanced extracellular proteostasis contributes to systemic host defence by maintaining a functional secreted proteome and avoiding proteotoxicity. A systematic analysis of the proteostasis network of secreted proteins in Caenorhabditis elegans identifies numerous regulators of protein homeostasis outside the cell, and highlights the contribution of extracellular proteostasis to host defence. |
| Databáze: | OpenAIRE |
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