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PMID: 18971375 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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.

Molecular biology of the cell ·Vol. 20 ·No. 1 ·2009-01-00 ·Pages 164-75

Scrimale T, Didone L, de Mesy Bentley KL, Krysan DJ

Abstract

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.

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
Chemicals
Calcium-Binding Proteins Intracellular Signaling Peptides and Proteins MID2 protein, S cerevisiae Membrane Glycoproteins Membrane Proteins SWI6 protein, S cerevisiae Saccharomyces cerevisiae Proteins Transcription Factors Mitogen-Activated Protein Kinases SLT2 protein, S cerevisiae
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Scrimale Thomas
Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Didone Louis
de Mesy Bentley Karen L
Krysan Damian J
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.e08-08-0809
Published
2009-01-00
Epub
2008-00-29
Pages
164-75
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC2613099
Subset
IM
Grants
NIAID NIH HHS · K08 AI062978 · United States
NIAID NIH HHS · K08AI062978 · United States
External Links
PubMed source DOI: 10.1091/mbc.e08-08-0809 PMC Full Text View journal details
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