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Mechanosensor-mediated Hsp70 phosphorylation orchestrates the landscape of the heat shock response

ABSTRACT: Yeast must respond rapidly to heat stress by activating multiple signaling pathways that preserve proteostasis. 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 co-ordinated 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 which includes altered interaction with Hsf1, multiple ribosomal subunits, the Bck1 MEK, and Edc3. Taken together these results provide a comprehensive, unified theory of the global yeast shock response that is mediated by the Hsp70 chaperone code.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Saccharomyces Cerevisiae (ncbitaxon:4932)

SUBMITTER: Luca Fornelli

PROVIDER: MSV000096492 | MassIVE | Thu Nov 21 13:53:00 GMT 2024

SECONDARY ACCESSION(S): PXD058151

REPOSITORIES: MassIVE

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