Expression of three topologically distinct membrane proteins elicits unique stress response pathways in the yeastSaccharomyces cerevisiae
| Autor: | Teresa M. Buck, Rick Jordan, Joshua L. Adelman, Patrick G. Needham, Thomas R. Kleyman, Jeffrey L. Brodsky, James Lyons-Weiler |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Epithelial sodium channel
Protein Folding Physiology Iron Cystic Fibrosis Transmembrane Conductance Regulator Saccharomyces cerevisiae Biology Regulon Model Organisms JUNQ and IPOD Stress Physiological Gene Expression Regulation Fungal Genetics Potassium Channels Inwardly Rectifying Epithelial Sodium Channels Secretory pathway Ion channel Gene Expression Profiling Endoplasmic reticulum Cell Membrane Membrane Proteins Reproducibility of Results Up-Regulation Cell biology Gene Ontology Membrane protein Unfolded protein response |
| Zdroj: | Physiological Genomics. 47:198-214 |
| ISSN: | 1531-2267 1094-8341 |
| DOI: | 10.1152/physiolgenomics.00101.2014 |
| Popis: | 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, the yeast iron regulon was activated. Nevertheless, a significant number of genes that respond to various environmental stressors were upregulated by all three substrates, and compared with previous microarray data we deduced the existence of a group of genes that reflect a novel misfolded membrane protein response. These data indicate that aberrant proteins in the ER elicit profound yet unique cellular responses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|