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Updated: Jan 8, 2026

Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Mechanosensor-mediated Hsp70 phosphorylation orchestrates the landscape of the heat shock response
Siddhi Omkar1, Jake T Kline2, James H Grissom1
1Department of Biological Sciences, The University of North Carolina at Charlotte, Charlotte, NC, USA.
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.
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