Role of the unfolded protein response pathway in secretory stress and regulation of INO1 expression in Saccharomyces cerevisiae

Genetics
Hak J ChangSusan A Henry

Abstract

The unfolded protein response pathway (UPR) enables the cell to cope with the buildup of unfolded proteins in the endoplasmic reticulum (ER). UPR loss-of-function mutants, hac1Delta and ire1Delta, are also inositol auxotrophs, a phenotype associated with defects in expression of INO1, the most highly regulated of a set of genes encoding enzymes of phospholipid metabolism. We now demonstrate that the UPR plays a functional role in membrane trafficking under conditions of secretory stress in yeast. Mutations conferring a wide range of membrane trafficking defects exhibited negative genetic interaction when combined with ire1Delta and hac1Delta. At semipermissive temperatures, carboxypeptidase Y transit time to the vacuole was slower in Sec(-) cells containing an ire1Delta or hac1Delta mutation than in Sec(-) cells with an intact UPR. The UPR was induced in Sec(-) cells defective in subcellular membrane trafficking events ranging from ER vesicle trafficking to distal secretion and in erg6Delta cells challenged with brefeldin A. However, the high levels of UPR induction observed under these conditions were not correlated with elevated INO1 expression. Indeed, many of the Sec(-) mutants that had elevated UPR expression at semipermis...Continue Reading

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Citations

May 27, 2009·Cellular and Molecular Life Sciences : CMLS·Ann-Hwee Lee, Laurie H Glimcher
Dec 8, 2010·Molecular Genetics and Genomics : MGG·Manuel J Villa-GarcíaSusan A Henry
Jun 15, 2007·Antonie van Leeuwenhoek·H Reynaldo López-Mirabal, Jakob R Winther
Mar 28, 2008·Current Hypertension Reports·Sepp D Kohlwein, Julia Petschnigg
Mar 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sumin HanAmy Chang
Jul 18, 2009·The Journal of Biological Chemistry·Julia PetschniggSepp D Kohlwein
Oct 10, 2008·The Journal of Biological Chemistry·Lilia R NunezSusan A Henry
Mar 15, 2011·Eukaryotic Cell·Yina WangChaoyang Xue
Mar 21, 2007·PLoS Pathogens·Guanggan HuJames W Kronstad
Dec 21, 2005·The Journal of Cell Biology·Thomas StrahlJeremy Thorner
Sep 11, 2008·Biotechnology and Bioengineering·Dagang HuangEric V Shusta
Aug 22, 2006·Biochimica Et Biophysica Acta·Maria L GasparSusan A Henry
Jan 15, 2014·Chemistry and Physics of Lipids·Susan A HenryStephen A Jesch
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Sep 11, 2019·The Journal of Biological Chemistry·Prabuddha DeyGeorge M Carman

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