Document Detail

The unfolded protein response is induced by the cell wall integrity mitogen-activated protein kinase signaling cascade and is required for cell wall integrity in Saccharomyces cerevisiae.
MedLine Citation:
PMID:  18971375     Owner:  NLM     Status:  MEDLINE    
The yeast cell wall is an extracellular structure that is dependent on secretory and membrane proteins for its construction. We investigated the role of protein quality control mechanisms in cell wall integrity and found that the unfolded protein response (UPR) and, to a lesser extent, endoplasmic reticulum (ER)-associated degradation (ERAD) pathways are required for proper cell wall construction. Null mutation of IRE1, double mutation of ERAD components (hrd1Delta and ubc7Delta) and ire1Delta, or expression of misfolded proteins show phenotypes similar to mutation of cell wall proteins, including hypersensitivity to cell wall-targeted molecules, alterations to cell wall protein layer, decreased cell wall thickness by electron microscopy, and increased cellular aggregation. Consistent with its important role in cell wall integrity, UPR is activated by signaling through the cell wall integrity mitogen-activated protein (MAP) kinase pathway during cell wall stress and unstressed vegetative growth. Both cell wall stress and basal UPR activity is mediated by Swi6p, a regulator of cell cycle and cell wall stress gene transcription, in a manner that is independent of its known coregulatory molecules. We propose that the cellular responses to ER and cell wall stress are coordinated to buffer the cell against these two related cellular stresses.
Thomas Scrimale; Louis Didone; Karen L de Mesy Bentley; Damian J Krysan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-10-29
Journal Detail:
Title:  Molecular biology of the cell     Volume:  20     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-01     Completed Date:  2009-03-27     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  164-75     Citation Subset:  IM    
Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
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MeSH Terms
Calcium-Binding Proteins / genetics,  metabolism
Cell Wall / chemistry,  metabolism*,  ultrastructure
Intracellular Signaling Peptides and Proteins
MAP Kinase Signaling System / physiology*
Membrane Glycoproteins
Membrane Proteins / genetics,  metabolism
Mitogen-Activated Protein Kinases / genetics,  metabolism*
Protein Conformation
Protein Denaturation*
Protein Folding
Saccharomyces cerevisiae* / cytology,  physiology
Saccharomyces cerevisiae Proteins / genetics,  metabolism
Stress, Physiological
Transcription Factors / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/MID2 protein, S cerevisiae; 0/Membrane Glycoproteins; 0/Membrane Proteins; 0/SWI6 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; 0/Transcription Factors; EC Protein Kinases; EC protein, S cerevisiae

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