Adaptation to Stressors by Systemic Protein Amyloidogenesis

Timothy E. Audas, Danielle E. Audas, Mathieu D. Jacob, J. J.David Ho, Mireille Khacho, Miling Wang, J. Kishan Perera, Caroline Gardiner, Clay A. Bennett, Trajen Head, Oleksandr N. Kryvenko, Mercé Jorda, Sylvia Daunert, Arun Malhotra, Laura Trinkle-Mulcahy, Mark L. Gonzalgo, Stephen Lee

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

The amyloid state of protein organization is typically associated with debilitating human neuropathies and is seldom observed in physiology. Here, we uncover a systemic program that leverages the amyloidogenic propensity of proteins to regulate cell adaptation to stressors. On stimulus, cells assemble the amyloid bodies (A-bodies), nuclear foci containing heterogeneous proteins with amyloid-like biophysical properties. A discrete peptidic sequence, termed the amyloid-converting motif (ACM), is capable of targeting proteins to the A-bodies by interacting with ribosomal intergenic noncoding RNA (rIGSRNA). The pathological β-amyloid peptide, involved in Alzheimer's disease, displays ACM-like activity and undergoes stimuli-mediated amyloidogenesis in vivo. Upon signal termination, elements of the heat-shock chaperone pathway disaggregate the A-bodies. Physiological amyloidogenesis enables cells to store large quantities of proteins and enter a dormant state in response to stressors. We suggest that cells have evolved a post-translational pathway that rapidly and reversibly converts native-fold proteins to an amyloid-like solid phase.

Original languageEnglish (US)
Pages (from-to)155-168
Number of pages14
JournalDevelopmental Cell
Volume39
Issue number2
DOIs
StatePublished - Oct 24 2016

Keywords

  • Hsp70
  • amyloid-bodies (A-bodies)
  • dormancy
  • extracellular stress
  • heat shock chaperones
  • long noncoding RNA (lncRNA)
  • physiological amyloidogenesis
  • β-amyloid

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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