RT Journal Article
SR Electronic
T1 Widespread remodelling of proteome solubility in response to different protein homeostasis stresses
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 692103
DO 10.1101/692103
A1 Xiaojing Sui
A1 Douglas E. V. Pires
A1 Shuai Nie
A1 Giulia Vecchi
A1 Michele Vendruscolo
A1 David B. Ascher
A1 Gavin E. Reid
A1 Danny M. Hatters
YR 2019
UL http://biorxiv.org/content/early/2019/07/26/692103.abstract
AB The accumulation of protein deposits in neurodegenerative diseases involves the presence of a metastable subproteome vulnerable to aggregation. To investigate this subproteome and the mechanisms that regulates it, we measured the proteome solubility of the Neuro2a cell line under protein homeostasis stresses induced by Huntington Disease proteotoxicity; Hsp70, Hsp90, proteasome and ER-mediated folding inhibition; and oxidative stress. We found one-quarter of the proteome extensively changed solubility. Remarkably, almost all the increases in insolubility were counteracted by increases in solubility of other proteins. Each stress directed a highly specific pattern of change, which reflected the remodelling of protein complexes involved in adaptation to perturbation, most notably stress granule proteins, which responded differently to different stresses. These results indicate that the robustness of protein homeostasis relies on the absence of proteins highly vulnerable to aggregation and on large changes in aggregation state of regulatory mechanisms that restore protein solubility upon specific perturbations.