An Hsp90 co-chaperone links protein folding and degradation and is part of a conserved protein quality control
Frederik Eisele,
Anna Maria Eisele-Bürger,
Xinxin Hao,
Lisa Larsson Berglund,
Johanna L. Höög,
Beidong Liu,
Thomas Nyström
Affiliations
Frederik Eisele
Institute for Biomedicine, Sahlgrenska Academy, Centre for Ageing and Health – AgeCap, University of Gothenburg, Medicinaregatan 7A, 413 90 Gothenburg, Sweden; Corresponding author
Anna Maria Eisele-Bürger
Institute for Biomedicine, Sahlgrenska Academy, Centre for Ageing and Health – AgeCap, University of Gothenburg, Medicinaregatan 7A, 413 90 Gothenburg, Sweden; Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences and Linnean Center for Plant Biology, PO Box 7015, 75007 Uppsala, Sweden
Xinxin Hao
Institute for Biomedicine, Sahlgrenska Academy, Centre for Ageing and Health – AgeCap, University of Gothenburg, Medicinaregatan 7A, 413 90 Gothenburg, Sweden
Lisa Larsson Berglund
Institute for Biomedicine, Sahlgrenska Academy, Centre for Ageing and Health – AgeCap, University of Gothenburg, Medicinaregatan 7A, 413 90 Gothenburg, Sweden; Department of Chemistry & Molecular Biology, University of Gothenburg, Medicinaregatan 9 C, 413 90 Gothenburg, Sweden
Johanna L. Höög
Department of Chemistry & Molecular Biology, University of Gothenburg, Medicinaregatan 9 C, 413 90 Gothenburg, Sweden
Beidong Liu
Department of Chemistry & Molecular Biology, University of Gothenburg, Medicinaregatan 9 C, 413 90 Gothenburg, Sweden
Thomas Nyström
Institute for Biomedicine, Sahlgrenska Academy, Centre for Ageing and Health – AgeCap, University of Gothenburg, Medicinaregatan 7A, 413 90 Gothenburg, Sweden; Corresponding author
Summary: In this paper, we show that the essential Hsp90 co-chaperone Sgt1 is a member of a general protein quality control network that links folding and degradation through its participation in the degradation of misfolded proteins both in the cytosol and the endoplasmic reticulum (ER). Sgt1-dependent protein degradation acts in a parallel pathway to the ubiquitin ligase (E3) and ubiquitin chain elongase (E4), Hul5, and overproduction of Hul5 partly suppresses defects in cells with reduced Sgt1 activity. Upon proteostatic stress, Sgt1 accumulates transiently, in an Hsp90- and proteasome-dependent manner, with quality control sites (Q-bodies) of both yeast and human cells that co-localize with Vps13, a protein that creates organelle contact sites. Misfolding disease proteins, such as synphilin-1 involved in Parkinson’s disease, are also sequestered to these compartments and require Sgt1 for their clearance.
