Adaptation to Stressors by Systemic Protein Amyloidogenesis

Dev Cell. 2016 Oct 24;39(2):155-168. doi: 10.1016/j.devcel.2016.09.002. Epub 2016 Oct 6.


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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological*
  • Amino Acid Motifs
  • Amyloid / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Biophysical Phenomena
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Female
  • Heat-Shock Response
  • Humans
  • MCF-7 Cells
  • Mice, Nude
  • Molecular Chaperones / metabolism
  • RNA, Untranslated / genetics
  • Ribosomes / metabolism
  • Stress, Physiological*


  • Amyloid
  • Amyloid beta-Peptides
  • Molecular Chaperones
  • RNA, Untranslated