Genomewide analysis reveals novel pathways affecting endoplasmic reticulum homeostasis, protein modification and quality control.
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.
Copic
Alenka
A
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Dorrington
Mariana
M
Pagant
Silvere
S
Barry
Justine
J
Lee
Marcus C S
MC
Singh
Indira
I
Hartman
John L
JL
Miller
Elizabeth A
EA
D000107:Acetylation; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016681:Genome, Fungal; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D008954:Models, Biological; D009154:Mutation; D017510:Protein Folding; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
C064922:ERD2 protein, S cerevisiae; D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D006657:Histones; C493530:Htz1 protein, S cerevisiae; C060153:KAR2 protein, yeast; D018000:Receptors, Peptide; D029701:Saccharomyces cerevisiae Proteins