Limited ER quality control for GPI-anchored proteins

被引:39
作者
Sikorska, Natalia [1 ,6 ]
Lemus, Leticia [1 ]
Aguilera-Romero, Auxiliadora [4 ,5 ]
Manzano-Lopez, Javier [2 ,3 ]
Riezman, Howard [4 ,5 ]
Muniz, Manuel [2 ,3 ]
Goder, Veit [1 ]
机构
[1] Univ Seville, Dept Genet, E-41012 Seville, Spain
[2] Univ Seville, Dept Cell Biol, E-41012 Seville, Spain
[3] Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla, Seville 41013, Spain
[4] Univ Geneva, Chem Biol, Natl Ctr Competence Res, CH-1211 Geneva 4, Switzerland
[5] Univ Geneva, Sci 2, Dept Biochem, CH-1211 Geneva 4, Switzerland
[6] Univ Strasbourg, CSIC, Inst Biol Mol Plantes, F-67081 Strasbourg, France
关键词
RETICULUM-ASSOCIATED DEGRADATION; ENDOPLASMIC-RETICULUM; SACCHAROMYCES-CEREVISIAE; SECRETORY PATHWAY; GOLGI; YEAST; TRAFFICKING; SUBSTRATE; TRANSPORT; UBIQUITIN;
D O I
10.1083/jcb.201602010
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Endoplasmic reticulum (ER) quality control mechanisms target terminally misfolded proteins for ER-associated degradation (ERAD). Misfolded glycophosphatidylinositol-anchored proteins (GPI-APs) are, however, generally poor ERAD substrates and are targeted mainly to the vacuole/lysosome for degradation, leading to predictions that a GPI anchor sterically obstructs ERAD. Here we analyzed the degradation of the misfolded GPI-AP Gas1* in yeast. We could efficiently route Gas1* to Hrd1-dependent ERAD and provide evidence that it contains a GPI anchor, ruling out that a GPI anchor obstructs ERAD. Instead, we show that the normally decreased susceptibility of Gas1* to ERAD is caused by canonical remodeling of its GPI anchor, which occurs in all GPI-APs and provides a protein-independent ER export signal. Thus, GPI anchor remodeling is independent of protein folding and leads to efficient ER export of even misfolded species. Our data imply that ER quality control is limited for the entire class of GPI-APs, many of them being clinically relevant.
引用
收藏
页码:693 / 704
页数:12
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