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

Martin C. Jonikas, Sean R. Collins, Vladimir Denic, Eugene Oh, Erin M. Quan, Volker Schmid, Jimena Weibezahn, Blanche Schwappach, Peter Walter, Jonathan S. Weissman, Maya Schuldiner

Research output: Contribution to journalArticlepeer-review

436 Scopus citations

Abstract

Protein folding in the endoplasmic reticuluiffis 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.

Original languageEnglish (US)
Pages (from-to)1693-1697
Number of pages5
JournalScience
Volume323
Issue number5922
DOIs
StatePublished - Mar 27 2009

All Science Journal Classification (ASJC) codes

  • General

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