Originally published as Genetics Published Articles Ahead of Print on May 11, 2009.

Genetics, Vol. 182, 757-769, July 2009, Copyright © 2009
doi:10.1534/genetics.109.101105

Genomewide Analysis Reveals Novel Pathways Affecting Endoplasmic Reticulum Homeostasis, Protein Modification and Quality Control

Alenka Copic*,1, Mariana Dorrington*,1, Silvere Pagant*,1, Justine Barry*, Marcus C. S. Lee{dagger}, Indira Singh{ddagger}, John L. Hartman, IV{ddagger} and Elizabeth A. Miller*,2

* Department of Biological Sciences, Columbia University, New York, New York 10027, {dagger} Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, and {ddagger} Department of Genetics, University of Alabama, Birmingham, Alabama 35294

2 Corresponding author: Columbia University, 1212 Amsterdam Ave., MC2456, NY, NY 10027.
E-mail: em2282{at}columbia.edu

To gain new mechanistic insight into ER homeostasis and the biogenesis of secretory proteins, we screened a genomewide collection of yeast mutants for defective intracellular retention of the ER chaperone, Kar2p. We identified 87 Kar2p-secreting strains, including a number of known components in secretory protein modification and sorting. Further characterization of the 73 nonessential Kar2p retention mutants revealed roles for a number of novel gene products in protein glycosylation, GPI-anchor attachment, ER quality control, and retrieval of escaped ER residents. A subset of these mutants, required for ER retrieval, included the GET complex and two novel proteins that likely function similarly in membrane insertion of tail-anchored proteins. Finally, the variant histone, Htz1p, and its acetylation state seem to play an important role in maintaining ER retrieval pathways, suggesting a surprising link between chromatin remodeling and ER homeostasis.


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Genetics 2009 182: NP. [Full Text]