Originally published as Genetics Published Articles Ahead of Print on January 21, 2007.

Genetics, Vol. 175, 1649-1664, April 2007, Copyright © 2007
doi:10.1534/genetics.106.066274

The Hsp40 Molecular Chaperone Ydj1p, Along With the Protein Kinase C Pathway, Affects Cell-Wall Integrity in the Yeast Saccharomyces cerevisiae

Christine M. Wright^*, Sheara W. Fewell^*, Mara L. Sullivan, James M. Pipas^*, Simon C. Watkins and Jeffrey L. Brodsky^*,1

^* Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260 and Center for Biological Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania 15261

¹ Corresponding author: Department of Biological Sciences, 274 Crawford Hall, University of Pittsburgh, Pittsburgh, PA 15260.
E-mail: jbrodsky{at}pitt.edu

Molecular chaperones, such as Hsp40, regulate cellular processes by aiding in the folding, localization, and activation of multi-protein machines. To identify new targets of chaperone action, we performed a multi-copy suppressor screen for genes that improved the slow-growth defect of yeast lacking the YDJ1 chromosomal locus and expressing a defective Hsp40 chimera. Among the genes identified were MID2, which regulates cell-wall integrity, and PKC1, which encodes protein kinase C and is linked to cell-wall biogenesis. We found that ydj1 yeast exhibit phenotypes consistent with cell-wall defects and that these phenotypes were improved by Mid2p or Pkc1p overexpression or by overexpression of activated downstream components in the PKC pathway. Yeast containing a thermosensitive allele in the gene encoding Hsp90 also exhibited cell-wall defects, and Mid2p or Pkc1p overexpression improved the growth of these cells at elevated temperatures. To determine the physiological basis for suppression of the ydj1 growth defect, wild-type and ydj1 yeast were examined by electron microscopy and we found that Mid2p overexpression thickened the mutant's cell wall. Together, these data provide the first direct link between cytoplasmic chaperone function and cell-wall integrity and suggest that chaperones orchestrate the complex biogenesis of this structure.

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