Mechanosensor-mediated Hsp70 phosphorylation orchestrates the landscape of the heat shock response
Year: 2025
Type: article
Abstract: Cells must respond rapidly to heat stress by activating multiple signaling pathways that preserve proteostasis. In budding yeast, this includes induction of Hsf1 and Msn2/4-mediated transcription, cell integrity signaling, stress-triggered phase separation of proteins, and inhibition of translation. How these pathways are so rapidly activated and coordinated remains unclear. We show that the mechanosensor Mid2 senses heat-induced membrane stretch and leads to rapid phosphorylation of the cytosolic Hsp70 Ssa1 at a well-conserved threonine (T492). Phosphorylation of T492 leads to epichaperome rearrangement promoting fine-tuning of multiple cellular processes including translational pausing, HSF activity, MAPK signaling and stress granule resolution. Taken together, these results provide a comprehensive, unified theory of the global yeast heat shock response mediated by the Hsp70 chaperone code.
Source: Nature Communications
Authors: Siddhi Omkar, Jake T. Kline, James H. Grissom, Diyun Sun, Richard J. Chi, Jared A. M. Bard, Luca Fornelli, Andrew W. Truman
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1324268608, G181895918, G2359393690, G2956300206, G4289365498, G5113422884, Exploring chaperone code control of TDP-43 function in ALS, Understanding SNX-BAR protein structure and function in yeast, Understanding the role of Hsp70 phosphorylation in proteostasis, A multi-level mass spectrometry pipeline for the analysis of whole proteoforms and their complexes
OpenAlex ID: W4417321440