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Genetics. 2009 Jul;182(3):757-69. doi: 10.1534/genetics.109.101105. Epub 2009 May 11.

Genomewide analysis reveals novel pathways affecting endoplasmic reticulum homeostasis, protein modification and quality control.

Author information

1
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

Abstract

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.

PMID:
19433630
PMCID:
PMC2710157
DOI:
10.1534/genetics.109.101105
[Indexed for MEDLINE]
Free PMC Article

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