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
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Research Support, N.I.H., Extramural
MeSH terms
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Acetylation
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Endoplasmic Reticulum / metabolism*
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Fungal Proteins / chemistry
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Genome, Fungal*
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Glycosylation
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Golgi Apparatus / metabolism
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HSP70 Heat-Shock Proteins / chemistry
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HSP70 Heat-Shock Proteins / genetics
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HSP70 Heat-Shock Proteins / metabolism
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Histones / genetics
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Histones / metabolism
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Homeostasis / physiology*
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Immunoblotting
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Immunoprecipitation
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Models, Biological
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Mutation
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Protein Folding
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Protein Processing, Post-Translational / physiology*
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Receptors, Peptide / genetics
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Receptors, Peptide / metabolism
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae / physiology
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Signal Transduction / genetics
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Signal Transduction / physiology*
Substances
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ERD2 protein, S cerevisiae
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Fungal Proteins
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HSP70 Heat-Shock Proteins
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Histones
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Htz1 protein, S cerevisiae
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KAR2 protein, yeast
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Receptors, Peptide
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Saccharomyces cerevisiae Proteins