Role of the Unfolded Protein Response Pathway in Secretory Stress and Regulation of INO1 Expression in Saccharomyces cerevisiae

摘要

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, hac1Δ and ire1Δ, 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 ire1Δ and hac1Δ. At semipermissive temperatures, carboxypeptidase Y transit time to the vacuole was slower in Sec⁻ cells containing an ire1Δ or hac1Δ 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 erg6Δ 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 semipermissive growth temperatures failed to achieve wild-type levels of INO1 expression under these same conditions.