Identification of novel extracellular chaperones

• Applicant: Dr. Della David
• Subject Area: Biochemistry ; Cell Biology
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 429529297

• Final Report Year: 2023

Final Report Abstract

In our previous work, we demonstrated the existence of a network of secreted proteins available to maintain extracellular proteostasis in the nematode C. elegans. In the present work, we expanded the evidence showing that enhancing extracellular proteostasis allows the animals to live longer and survive better during a pathogenic attack. We investigated the mechanism of action of C. elegans extracellular regulators of protein aggregation. We identified one regulator that acts as an extracellular chaperone with holdase activity, the first of its kind to be discovered in C. elegans. Moreover, we found evidence for anti-aggregation activity in a human protein with homologies to a newly identified C. elegans extracellular regulator. Overall, our results highlight the potential of novel extracellular proteostasis modulators initially discovered in C. elegans and their corresponding human orthologs.

Publications

• Extracellular proteostasis prevents aggregation during pathogenic attack. Nature, 584(7821), 410-414.
  Gallotta, Ivan; Sandhu, Aneet; Peters, Maximilian; Haslbeck, Martin; Jung, Raimund; Agilkaya, Sinem; Blersch, Jane L.; Rödelsperger, Christian; Röseler, Waltraud; Huang, Chaolie; Sommer, Ralf J. & David, Della C.
  
• Tissue-specific safety mechanism results in opposite protein aggregation patterns during aging. (2020, 12, 4). American Geophysical Union (AGU).
  Jung, Raimund; Lechler, Marie C.; Rödelsperger, Christian; Röseler, Waltraud; Sommer, Ralf J. & David, Della C.