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

Thomas Scrimale; Louis Didone; Karen L de Mesy Bentley; Damian J Krysan

doi:10.1091/mbc.E08-08-0809

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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

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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

Thomas Scrimale, Louis Didone, Karen L de Mesy Bentley and Damian J Krysan

Molecular biology of the cell, Vol.20(1), pp.164-175

01/2009

DOI: 10.1091/mbc.E08-08-0809

PMCID: PMC2613099

PMID: 18971375

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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.

Calcium-Binding Proteins - metabolism

MAP Kinase Signaling System - physiology

Saccharomyces cerevisiae - physiology

Membrane Proteins - genetics

Stress, Physiological

Intracellular Signaling Peptides and Proteins

Cell Wall - chemistry

Saccharomyces cerevisiae Proteins - genetics

Transcription Factors - genetics

Protein Folding

Saccharomyces cerevisiae - cytology

Transcription Factors - metabolism

Cell Wall - metabolism

Protein Denaturation

Saccharomyces cerevisiae Proteins - metabolism

Mitogen-Activated Protein Kinases - genetics

Protein Conformation

Membrane Proteins - metabolism

Membrane Glycoproteins

Cell Wall - ultrastructure

Calcium-Binding Proteins - genetics

Mitogen-Activated Protein Kinases - metabolism

Details

Title: Subtitle: 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
Creators: Thomas Scrimale - Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
Louis Didone
Karen L de Mesy Bentley
Damian J Krysan
Resource Type: Journal article
Publication Details: Molecular biology of the cell, Vol.20(1), pp.164-175
DOI: 10.1091/mbc.E08-08-0809
PMID: 18971375
PMCID: PMC2613099
NLM abbreviation: Mol Biol Cell
ISSN: 1059-1524
eISSN: 1939-4586
Grant note: K08 AI062978 / NIAID NIH HHS K08AI062978 / NIAID NIH HHS
Language: English
Date published: 01/2009
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
Record Identifier: 9984093350702771

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