Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 27 March 2009:
Vol. 323. no. 5922, pp. 1693 - 1697
DOI: 10.1126/science.1167983
Prev | Table of Contents | Next

Research Articles

Comprehensive Characterization of Genes Required for Protein Folding in the Endoplasmic Reticulum

Martin C. Jonikas,1,2,3,4 Sean R. Collins,1,3,4 Vladimir Denic,1,3,4* Eugene Oh,1,3,4 Erin M. Quan,1,3,4 Volker Schmid,5 Jimena Weibezahn,1,3,4 Blanche Schwappach,5 Peter Walter,2,3 Jonathan S. Weissman,1,3,4{dagger} Maya Schuldiner1,3,4{ddagger}

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.

1 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
2 Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.
3 Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
4 California Institute for Quantitative Biomedical Research, San Francisco, CA 94143, USA.
5 Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.

* Present address: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.

{ddagger} Present address: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.

{dagger} To whom correspondence should be addressed. E-mail: weissman{at}cmp.ucsf.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Biogenesis of tail-anchored proteins: the beginning for the end?.
C. Rabu, V. Schmid, B. Schwappach, and S. High (2009)
J. Cell Sci. 122, 3605-3612
   Abstract »    Full Text »    PDF »
Model for eukaryotic tail-anchored protein binding based on the structure of Get3.
C. J. M. Suloway, J. W. Chartron, M. Zaslaver, and W. M. Clemons Jr. (2009)
PNAS 106, 14849-14854
   Abstract »    Full Text »    PDF »
Genomewide Analysis Reveals Novel Pathways Affecting Endoplasmic Reticulum Homeostasis, Protein Modification and Quality Control.
A. Copic, M. Dorrington, S. Pagant, J. Barry, M. C. S. Lee, I. Singh, J. L. Hartman IV, and E. A. Miller (2009)
Genetics 182, 757-769
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)