Expression of three topologically distinct membrane proteins elicits unique stress response pathways in the yeast Saccharomyces cerevisiae

Physiological Genomics
Teresa M BuckJeffrey L Brodsky

Abstract

Misfolded membrane proteins are retained in the endoplasmic reticulum (ER) and are subject to ER-associated degradation, which clears the secretory pathway of potentially toxic species. While the transcriptional response to environmental stressors has been extensively studied, limited data exist describing the cellular response to misfolded membrane proteins. To this end, we expressed and then compared the transcriptional profiles elicited by the synthesis of three ER retained, misfolded ion channels: The α-subunit of the epithelial sodium channel, ENaC, the cystic fibrosis transmembrane conductance regulator, CFTR, and an inwardly rectifying potassium channel, Kir2.1, which vary in their mass, membrane topologies, and quaternary structures. To examine transcriptional profiles in a null background, the proteins were expressed in yeast, which was previously used to examine the degradation requirements for each substrate. Surprisingly, the proteins failed to induce a canonical unfolded protein response or heat shock response, although messages encoding several cytosolic and ER lumenal protein folding factors rose when αENaC or CFTR was expressed. In contrast, the levels of these genes were unaltered by Kir2.1 expression; instead,...Continue Reading

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Citations

Nov 18, 2016·Journal of Industrial Microbiology & Biotechnology·Naurú Idalia Vargas-MayaJuan Carlos Torres-Guzmán
Oct 4, 2017·The Journal of Biological Chemistry·Ligia Acosta-SampsonJamie H D Cate
Jun 20, 2018·Current Opinion in Nephrology and Hypertension·Teresa M Buck, Jeffrey L Brodsky
Sep 20, 2018·The Journal of Biological Chemistry·Shaohu ShengThomas R Kleyman
Sep 21, 2019·The Journal of Cell Biology·Zhihao Sun, Jeffrey L Brodsky
Apr 15, 2020·Current Protocols in Protein Science·Lucile GuyotRenaud Wagner

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