The Hsp110 protein chaperone Sse1 is required for yeast cell wall integrity and morphogenesis.
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 sse1Delta and sti1Delta 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 sse1Delta 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.
Shaner
Lance
L
Department of Microbiology and Molecular Genetics, University of Texas Medical School, 6431 Fannin Street, Houston, TX 77030, USA.
Gibney
Patrick A
PA
Morano
Kevin A
KA
D002473:Cell Wall / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009024:Morphogenesis; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D005656:Fungal Proteins; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C074510:HSP82 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C090869:SSA3 protein, S cerevisiae; C494656:SSE1 protein, S cerevisiae; C542289:STI1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae