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
来源
JOURNAL OF CELL BIOLOGY | 2016年 / 213卷 / 06期
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
相关论文
共 50 条
  • [41] INTRACELLULAR-TRANSPORT OF GPI-ANCHORED PROTEINS BY YEAST
    RIEZMAN, H
    HORVATH, A
    MANNINGKRIEG, U
    MOVVA, R
    BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, 1994, 27 (02) : 323 - 326
  • [42] Cell-surface engineering with GPI-anchored proteins
    Medof, ME
    Nagarajan, S
    Tykocinski, ML
    FASEB JOURNAL, 1996, 10 (05): : 574 - 586
  • [43] Dynamics of GPI-anchored proteins on the surface of living cells
    Nohe, Anja
    Keating, Eleonora
    Fivaz, Marc
    van der Goot, F. Gisou
    Petersen, Nils O.
    NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, 2006, 2 (01) : 1 - 7
  • [44] Differential sorting and fate of endocytosed GPI-anchored proteins
    Fivaz, M
    Vilbois, F
    Thurnheer, S
    Pasquali, C
    Abrami, L
    Bickel, PE
    Parton, RG
    van der Goot, FG
    EMBO JOURNAL, 2002, 21 (15): : 3989 - 4000
  • [45] The role of GPI-anchored proteins in chondrogenesis and cell polarity
    Ahrens, Molly J.
    Dudley, Andrew T.
    DEVELOPMENTAL BIOLOGY, 2008, 319 (02) : 482 - 482
  • [46] Lipid remodeling of GPI-anchored proteins and its function
    Fujita, Morihisa
    Jigami, Yoshifumi
    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2008, 1780 (03): : 410 - 420
  • [47] Signal transduction via GPI-anchored membrane proteins
    Robinson, PJ
    ADP-RIBOSYLATION IN ANIMAL TISSUES: STRUCTURE, FUNCTION, AND BIOLOGY OF MONO (ADP-RIBOSYL) TRANSFERASES AND RELATED ENZYMES, 1997, 419 : 365 - 370
  • [48] Microdomains in lymphocyte signalling: beyond GPI-anchored proteins
    Ilangumaran, S
    He, HT
    Hoessli, DC
    IMMUNOLOGY TODAY, 2000, 21 (01): : 2 - 7
  • [49] ABNORMALITIES IN THE SECRETORY PATHWAY OF GPI-ANCHORED PROTEINS IN SCHIZOPHRENIA
    Kim, Pitna
    Haroutunian, Vahram
    Meador-Woodruff, James
    SCHIZOPHRENIA BULLETIN, 2017, 43 : S197 - S197
  • [50] Human SND2 mediates ER targeting of GPI-anchored proteins with low hydrophobic GPI attachment signals
    Yang, Jing
    Hirata, Tetsuya
    Liu, Yi-Shi
    Guo, Xin-Yu
    Gao, Xiao-Dong
    Kinoshita, Taroh
    Fujita, Morihisa
    FEBS LETTERS, 2021, 595 (11) : 1542 - 1558