Adaptation to stressors by Systemic Protein Amyloidogenesis
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| Authors: | Audas, TE; Audas, DE; Jacob, MD; Ho, JJD; Khacho, M; Wang, ML; Perera, JK; Gardiner, C; Bennett, CA; Head, T; Kryvenko, ON; Jorda, M; Daunert, S; Malhotra, A; Trinkle-Mulcahy, L; Gonzalgo, ML; Lee, S |
| Year: | 2016 |
| Journal: | Developmental Cell 39: 155-168 Article Link (DOI) |
| Title: | Adaptation to stressors by Systemic Protein Amyloidogenesis |
| 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 beta-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. |
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