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

TY - JOUR

T1 - Genomewide analysis reveals novel pathways affecting endoplasmic eticulum homeostasis, protein modification and quality control

AU - Čopič, Alenka

AU - Dorrington, Mariana

AU - Pagant, Silvere

AU - Barry, Justine

AU - Lee, Marcus C.S.

AU - Singh, Indira

AU - Hartman IV, John L.

AU - Miller, Elizabeth A.

PY - 2009/7/1

Y1 - 2009/7/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/70349318145

U2 - 10.1534/genetics.109.101105

DO - 10.1534/genetics.109.101105

M3 - Article

C2 - 19433630

AN - SCOPUS:70349318145

SN - 0016-6731

VL - 182

SP - 757

EP - 769

JO - Genetics

JF - Genetics

IS - 3

ER -