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 Kryvenko, Merce Jorda, Sylvia Daunert, Arun Malhotra, Laura Trinkle-Mulcahy, Mark L Gonzalgo, Stephen Lee

Research output: Contribution to journalArticle

38 Citations (Scopus)

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

Fingerprint

Amyloidogenic Proteins
Amyloid
Proteins
Protein Transport
Shock
Alzheimer Disease
Hot Temperature
Peptides
Physiology

Keywords

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

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Audas, T. E., Audas, D. E., Jacob, M. D., Ho, J. J. D., Khacho, M., Wang, M., ... Lee, S. (2016). Adaptation to Stressors by Systemic Protein Amyloidogenesis. Developmental Cell, 39(2), 155-168. https://doi.org/10.1016/j.devcel.2016.09.002

Adaptation to Stressors by Systemic Protein Amyloidogenesis. / Audas, Timothy E.; Audas, Danielle E.; Jacob, Mathieu D.; Ho, J. J David; Khacho, Mireille; Wang, Miling; Perera, J. Kishan; Gardiner, Caroline; Bennett, Clay A.; Head, Trajen; Kryvenko, Oleksandr; Jorda, Merce; Daunert, Sylvia; Malhotra, Arun; Trinkle-Mulcahy, Laura; Gonzalgo, Mark L; Lee, Stephen.

In: Developmental Cell, Vol. 39, No. 2, 24.10.2016, p. 155-168.

Research output: Contribution to journalArticle

Audas, TE, Audas, DE, Jacob, MD, Ho, JJD, Khacho, M, Wang, M, Perera, JK, Gardiner, C, Bennett, CA, Head, T, Kryvenko, O, Jorda, M, Daunert, S, Malhotra, A, Trinkle-Mulcahy, L, Gonzalgo, ML & Lee, S 2016, 'Adaptation to Stressors by Systemic Protein Amyloidogenesis', Developmental Cell, vol. 39, no. 2, pp. 155-168. https://doi.org/10.1016/j.devcel.2016.09.002
Audas TE, Audas DE, Jacob MD, Ho JJD, Khacho M, Wang M et al. Adaptation to Stressors by Systemic Protein Amyloidogenesis. Developmental Cell. 2016 Oct 24;39(2):155-168. https://doi.org/10.1016/j.devcel.2016.09.002
Audas, Timothy E. ; Audas, Danielle E. ; Jacob, Mathieu D. ; Ho, J. J David ; Khacho, Mireille ; Wang, Miling ; Perera, J. Kishan ; Gardiner, Caroline ; Bennett, Clay A. ; Head, Trajen ; Kryvenko, Oleksandr ; Jorda, Merce ; Daunert, Sylvia ; Malhotra, Arun ; Trinkle-Mulcahy, Laura ; Gonzalgo, Mark L ; Lee, Stephen. / Adaptation to Stressors by Systemic Protein Amyloidogenesis. In: Developmental Cell. 2016 ; Vol. 39, No. 2. pp. 155-168.
@article{6befa281040d425b9296cd3ca594f1e8,
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 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 = "amyloid-bodies (A-bodies), dormancy, extracellular stress, heat shock chaperones, Hsp70, long noncoding RNA (lncRNA), physiological amyloidogenesis, β-amyloid",
author = "Audas, {Timothy E.} and Audas, {Danielle E.} and Jacob, {Mathieu D.} and Ho, {J. J David} and Mireille Khacho and Miling Wang and Perera, {J. Kishan} and Caroline Gardiner and Bennett, {Clay A.} and Trajen Head and Oleksandr Kryvenko and Merce Jorda and Sylvia Daunert and Arun Malhotra and Laura Trinkle-Mulcahy and Gonzalgo, {Mark L} and Stephen Lee",
year = "2016",
month = "10",
day = "24",
doi = "10.1016/j.devcel.2016.09.002",
language = "English (US)",
volume = "39",
pages = "155--168",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Adaptation to Stressors by Systemic Protein Amyloidogenesis

AU - Audas, Timothy E.

AU - Audas, Danielle E.

AU - Jacob, Mathieu D.

AU - Ho, J. J David

AU - Khacho, Mireille

AU - Wang, Miling

AU - Perera, J. Kishan

AU - Gardiner, Caroline

AU - Bennett, Clay A.

AU - Head, Trajen

AU - Kryvenko, Oleksandr

AU - Jorda, Merce

AU - Daunert, Sylvia

AU - Malhotra, Arun

AU - Trinkle-Mulcahy, Laura

AU - Gonzalgo, Mark L

AU - Lee, Stephen

PY - 2016/10/24

Y1 - 2016/10/24

N2 - 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.

AB - 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.

KW - amyloid-bodies (A-bodies)

KW - dormancy

KW - extracellular stress

KW - heat shock chaperones

KW - Hsp70

KW - long noncoding RNA (lncRNA)

KW - physiological amyloidogenesis

KW - β-amyloid

UR - http://www.scopus.com/inward/record.url?scp=84992053042&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992053042&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2016.09.002

DO - 10.1016/j.devcel.2016.09.002

M3 - Article

VL - 39

SP - 155

EP - 168

JO - Developmental Cell

JF - Developmental Cell

SN - 1534-5807

IS - 2

ER -