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The Hsp110 protein chaperone Sse1 is required for yeast cell wall integrity and morphogenesis

Abstract

Molecular chaperones direct refolding and triage decisions and support signal transduction responses to cytotoxic stress. The eukaryotic chaperone Hsp110 is represented by the SSE1/2 genes in Saccharomyces cerevisiae, which act as nucleotide exchange factors (NEFs) for cognate cytosolic Hsp70 chaperones. In this report, we present evidence that Sse1 is required for signaling through the cell integrity pathway via partnership with Hsp90 and the terminal MAP kinase Slt2. We found that sse1Δ and sti1Δ mutant cells share the typical cell integrity mutant phenotypes of osmoremediated temperature-sensitive growth and sensitivity to cell wall-damaging agents. Sse1 binds to Slt2 in vivo and similar to Hsp90 mutants, Slt2 stability and phosphorylation is not compromised in sse1Δ cells, whereas activation of the downstream transcription factor Rlm1 is abolished. In addition to Rlm1, Slt2 activates the Swi4/Swi6 heterodimer SBF in response to cell wall damage. SSE1 displayed dramatic synthetic phenotypes when disrupted in combination with mutations in SBF and the related Mbp1/Swi6 heterodimer MBF, characterized by severe growth and morphological defects. These defects were reversed by restoration of Hsp70 NEF activity, providing a mechanistic model wherein Sse1 functionally partners with Hsp90 as an Hsp70 NEF to promote client protein maturation and interaction with downstream effectors.

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Acknowledgments

We thank Drs. Brenda Andrews, Jeffrey Brodsky, Betty Craig, Peter Piper, and Jill Johnson for advice, reagents, and helpful discussion. We also thank Dr. William Margolin for microscopy support. This work was supported by National Institutes of Health grant GM074696 to K.A.M.

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Correspondence to Kevin A. Morano.

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Lance Shaner and Patrick A. Gibney contributed equally to this article.

Communicated by S. Hohmann.

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Shaner, L., Gibney, P.A. & Morano, K.A. The Hsp110 protein chaperone Sse1 is required for yeast cell wall integrity and morphogenesis. Curr Genet 54, 1 (2008). https://doi.org/10.1007/s00294-008-0193-y

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  • DOI: https://doi.org/10.1007/s00294-008-0193-y

Key words

  • Yeast
  • Heat shock
  • Morphogenesis
  • Cell integrity
  • Chaperone
  • Hsp110
  • Hsp70
  • Hsp90