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.
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.
Scrimale
Thomas
T
Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Didone
Louis
L
de Mesy Bentley
Karen L
KL
Krysan
Damian J
DJ
D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C091625:MID2 protein, S cerevisiae; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C075111:SWI6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae