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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Endoplasmic Reticulum / metabolism*
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Genome, Fungal*
  • Glycosylation
  • Golgi Apparatus / metabolism
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Histones / genetics
  • Histones / metabolism
  • Homeostasis / physiology*
  • Immunoblotting
  • Immunoprecipitation
  • Models, Biological
  • Mutation
  • Protein Folding
  • Protein Processing, Post-Translational / physiology*
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology*

Substances

  • ERD2 protein, S cerevisiae
  • Fungal Proteins
  • HSP70 Heat-Shock Proteins
  • Histones
  • Htz1 protein, S cerevisiae
  • KAR2 protein, yeast
  • Receptors, Peptide
  • Saccharomyces cerevisiae Proteins