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@ARTICLE{Gallotta:153430,
      author       = {Gallotta, Ivan and Sandhu, Aneet and Peters, Maximilian and
                      Haslbeck, Martin and Jung, Raimund and Agilkaya, Sinem and
                      Blersch, Jane L. and Rödelsperger, Christian and Röseler,
                      Waltraud and Huang, Chaolie and Sommer, Ralf J. and David,
                      Della},
      title        = {{E}xtracellular proteostasis prevents aggregation during
                      pathogenic attack},
      journal      = {Nature / Physical science},
      volume       = {584},
      number       = {7821},
      issn         = {1476-4687},
      address      = {London},
      publisher    = {Macmillan28177},
      reportid     = {DZNE-2020-01427},
      pages        = {410 - 414},
      year         = {2020},
      abstract     = {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 proteins1,2,3,4,5. 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 pathogens6,7,8,9,
                      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.},
      keywords     = {Aging: metabolism / Animals / Caenorhabditis elegans:
                      cytology / Caenorhabditis elegans: genetics / Caenorhabditis
                      elegans: metabolism / Caenorhabditis elegans: microbiology /
                      Caenorhabditis elegans Proteins: metabolism / Extracellular
                      Space: metabolism / Fatty Acid-Binding Proteins: metabolism
                      / MAP Kinase Signaling System / Protein Aggregates / Protein
                      Aggregation, Pathological: prevention $\&$ control /
                      Proteome: genetics / Proteome: metabolism / Proteostasis /
                      RNA Interference},
      cin          = {AG David},
      ddc          = {530},
      cid          = {I:(DE-2719)1210004},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32641833},
      doi          = {10.1038/s41586-020-2461-z},
      url          = {https://pub.dzne.de/record/153430},
}