The acyltransferase, Gpc1, is regulated by the unfolded protein response in Saccharomyces cerevisiae

Abstract

The unfolded protein response (UPR) is a proteostatic process is in which unfolded and misfolded proteins are degraded or modified. The UPR is initiated by abnormal proteins binding to the membrane protein Ire1, which dimerizes to become active and then splices the transcription factor Hac1. Spliced Hac1 produces a transcriptional response in downstream genes related to protein folding, secretion, and degradation. In addition, studies show that the UPR can be activated by endoplasmic reticulum (ER) membrane stress and can impact the expression of genes involved in lipid metabolism. Membrane abberancies that can activate the UPR include altered lipid composition and membrane fluidity. We have identified a glycerophosphocholine acyltransferase, Gpc1, that contributes to phosphatidylcholine (PC) synthesis in Saccharomyces cerevisiae and impacts PC species saturation. Gpc1 participates in the PC Deacylation-Reacylation Pathway (PC-DRP). In PC-DRP, PC is first completely deacylated by type B phospholipases, yielding glycerophosphocholine, which is then reacylated by Gpc1 to form lysophosphotidylcholine. Finally, a second acylation by Ale1 generates a PC molecule. Notably, our data demonstrate that Gpc1 produces more saturated PC species, potentially impacting membrane fluidity. Here, we report that GPC1 expressionis upregulated by UPR inducers such as tunicamycin and that loss of Gpc1 leads to increased sensitivity to tunicamycin. Additionally, loss of GPC1 is shown to activate the UPR based on expression of KAR2, a known UPR target. Ongoing studies include an examination of other constituents of PC-DRP are their relationship to the UPR.