Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum.
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.
Jonikas
Martin C
MC
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
Collins
Sean R
SR
Denic
Vladimir
V
Oh
Eugene
E
Quan
Erin M
EM
Schmid
Volker
V
Weibezahn
Jimena
J
Schwappach
Blanche
B
Walter
Peter
P
Weissman
Jonathan S
JS
Schuldiner
Maya
M