Quantitative glycoproteomics reveals cellular substrate selectivity of the ER protein quality control sensors UGGT1 and UGGT2

被引:29
作者
Adams, Benjamin M. [1 ,2 ]
Canniff, Nathan P. [1 ,2 ]
Guay, Kevin P. [1 ,2 ]
Larsen, Ida Signe Bohse [3 ,4 ]
Hebert, Daniel N. [1 ,2 ]
机构
[1] Univ Massachusetts, Dept Biochem & Mol Biol, Amherst, MA 01003 USA
[2] Univ Massachusetts, Program Mol & Cellular Biol, Amherst, MA 01003 USA
[3] Univ Copenhagen, Dept Cellular & Mol Med, Copenhagen, Denmark
[4] Univ Copenhagen, Copenhagen Ctr Glyc, Copenhagen, Denmark
来源
ELIFE | 2020年 / 9卷
关键词
N-LINKED GLYCANS; UDP-GLUCOSEGLYCOPROTEIN GLUCOSYLTRANSFERASE; MISFOLDED GLYCOPROTEINS; CALNEXIN BINDING; GLYCOSYLATION; EXPRESSION; OLIGOSACCHARIDES; REGLUCOSYLATION; CALRETICULIN; DEGRADATION;
D O I
10.7554/eLife.63997
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
UDP-glucose:glycoprotein glucosyltransferase (UGGT) 1 and 2 are central hubs in the chaperone network of the endoplasmic reticulum (ER), acting as gatekeepers to the early secretory pathway, yet little is known about their cellular clients. These two quality control sensors control lectin chaperone binding and glycoprotein egress from the ER. A quantitative glycoproteomics strategy was deployed to identify cellular substrates of the UGGTs at endogenous levels in CRISPR-edited HEK293 cells. The 71 UGGT substrates identified were mainly large multidomain and heavily glycosylated proteins when compared to the general N-glycoproteome. UGGT1 was the dominant glucosyltransferase with a preference toward large plasma membrane proteins whereas UGGT2 favored the modification of smaller, soluble lysosomal proteins. This study sheds light on differential specificities and roles of UGGT1 and UGGT2 and provides insight into the cellular reliance on the carbohydrate-dependent chaperone system to facilitate proper folding and maturation of the cellular N-glycoproteome.
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页数:27
相关论文
共 81 条
  • [1] Proper secretion of the serpin antithrombin relies strictly on thiol-dependent quality control
    Adams, Benjamin M.
    Ke, Haiping
    Gierasch, Lila M.
    Gershenson, Anne
    Hebert, Daniel N.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2019, 294 (50) : 18992 - 19011
  • [2] Protein Quality Control in the Endoplasmic Reticulum
    Adams, Benjamin M.
    Oster, Michela E.
    Hebert, Daniel N.
    [J]. PROTEIN JOURNAL, 2019, 38 (03) : 317 - 329
  • [3] N-linked protein glycosylation in the ER
    Aebi, Markus
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2013, 1833 (11): : 2430 - 2437
  • [4] [Anonymous], 2008, COLD SPRING HARB PRO
  • [5] Two homologues encoding human UDP-glucose:glycoprotein glucosyltransferase differ in mRNA expression and enzymatic activity
    Arnold, SM
    Fessler, LI
    Fessler, JH
    Kaufman, RJ
    [J]. BIOCHEMISTRY, 2000, 39 (09) : 2149 - 2163
  • [6] The noncatalytic portion of human UDP-glucose:glycoprotein glucosyltransferase I confers UDP-glucose binding and transferase function to the catalytic domain
    Arnold, SM
    Kaufman, RJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (44) : 43320 - 43328
  • [7] Bajaj L, 2020, J CLIN INVEST, V130, P4118, DOI [10.1172/JCl130955, 10.1172/JCI130955]
  • [8] BAKSH S, 1991, J BIOL CHEM, V266, P21458
  • [9] Recent advances in understanding catalysis of protein folding by molecular chaperones
    Balchin, David
    Hayer-Hartl, Manajit
    Hartl, F. Ulrich
    [J]. FEBS LETTERS, 2020, 594 (17) : 2770 - 2781
  • [10] In vivo aspects of protein folding and quality control
    Balchin, David
    Hayer-Hartl, Manajit
    Hartl, F. Ulrich
    [J]. SCIENCE, 2016, 353 (6294)