Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum.

TitleComprehensive characterization of genes required for protein folding in the endoplasmic reticulum.
Publication TypeJournal Article
Year of Publication2009
AuthorsJonikas, MC, Collins, SR, Denic, V, Oh, E, Quan, EM, Schmid, V, Weibezahn, J, Schwappach, B, Walter, P, Weissman, JS, Schuldiner, M
JournalScience
Volume323
Issue5922
Pagination1693-7
Date Published2009 Mar 27
ISSN1095-9203
KeywordsEndoplasmic Reticulum, Epistasis, Genetic, Gene Deletion, Gene Expression Regulation, Fungal, Genes, Fungal, Genes, Reporter, Membrane Proteins, Mutation, Phenotype, Protein Folding, Protein Processing, Post-Translational, Protein Structure, Tertiary, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Secretory Pathway
Abstract

<p>Protein folding in the endoplasmic reticulum is a complex process whose malfunction is implicated in disease and aging. By using the cell's endogenous sensor (the unfolded protein response), we identified several hundred yeast genes with roles in endoplasmic reticulum folding and systematically characterized their functional interdependencies by measuring unfolded protein response levels in double mutants. This strategy revealed multiple conserved factors critical for endoplasmic reticulum folding, including an intimate dependence on the later secretory pathway, a previously uncharacterized six-protein transmembrane complex, and a co-chaperone complex that delivers tail-anchored proteins to their membrane insertion machinery. The use of a quantitative reporter in a comprehensive screen followed by systematic analysis of genetic dependencies should be broadly applicable to functional dissection of complex cellular processes from yeast to human.</p>

DOI10.1126/science.1167983
Alternate JournalScience
PubMed ID19325107
PubMed Central IDPMC2877488
Grant List081671 / / Wellcome Trust / United Kingdom
/ / Howard Hughes Medical Institute / United States
/ / Howard Hughes Medical Institute / United States