Editors' ChoiceCell Biology

Folding Forum

Science Signaling  31 Mar 2009:
Vol. 2, Issue 64, pp. ec117
DOI: 10.1126/scisignal.264ec117

The endoplasmic reticulum (ER) establishes and maintains a specialized environment capable of supporting the folding of secreted proteins. Reductionist approaches have focused on understanding the mechanism and biological role of a specific chaperone or degradation system in isolation. Jonikas et al. present a complementary strategy using the cell’s endogenous sensor of misfolding in the ER (the Ire1/Hac1 system) as a reporter to identify all the genes that contribute to ER folding. A remarkable array of different factors and processes were seen to contribute to ER folding. Measuring induction of the unfolded-protein response pathway in double mutants allowed the equivalent of hundreds of secondary screens in parallel and the systematic functional dissection of previously characterized and uncharacterized processes needed for proper ER function.

M. C. Jonikas, S. R. Collins, V. Denic, E. Oh, E. M. Quan, V. Schmid, J. Weibezahn, B. Schwappach, P. Walter, J. S. Weissman, M. Schuldiner, Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum. Science 323, 1693–1697 (2009). [Abstract] [Full Text]