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

Adaptation to Stressors by Systemic Protein Amyloidogenesis.

Author information

1
Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
2
Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Urology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
3
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
4
Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
5
Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Urology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
6
Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
7
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Urology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Pathology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
8
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
9
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Urology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
10
Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Department of Urology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: stephenlee@med.miami.edu.

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.

KEYWORDS:

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

PMID:
27720612
PMCID:
PMC5098424
DOI:
10.1016/j.devcel.2016.09.002
[Indexed for MEDLINE]
Free PMC Article

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