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

Alenka Čopič, Mariana Dorrington, Silvere Pagant, Justine Barry, Marcus C.S. Lee, Indira Singh, John L. Hartman IV, Elizabeth A. Miller (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

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, GPIanchor 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.

Original languageEnglish
Pages (from-to)757-769
Number of pages13
JournalGenetics
Volume182
Issue number3
DOIs
Publication statusPublished - 1 Jul 2009

ASJC Scopus subject areas

  • Genetics

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