A cell-based reglucosylation assay demonstrates the role of GT1 in the quality control of a maturing glycoprotein.

The Journal of Cell Biology
Bradley R PearseDaniel N Hebert

Abstract

The endoplasmic reticulum (ER) protein GT1 (UDP-glucose: glycoprotein glucosyltransferase) is the central enzyme that modifies N-linked carbohydrates based upon the properties of the polypeptide backbone of the maturing substrate. GT1 adds glucose residues to nonglucosylated proteins that fail the quality control test, supporting ER retention through persistent binding to the lectin chaperones calnexin and calreticulin. How GT1 functions in its native environment on a maturing substrate is poorly understood. We analyzed the reglucosylation of a maturing model glycoprotein, influenza hemagglutinin (HA), in the intact mammalian ER. GT1 reglucosylated N-linked glycans in the slow-folding stem domain of HA once the nascent chain was released from the ribosome. Maturation mutants that disrupted the oxidation or oligomerization of HA also supported region-specific reglucosylation by GT1. Therefore, GT1 acts as an ER quality control sensor by posttranslationally reglucosylating glycans on slow-folding or nonnative domains to recruit chaperones specifically to critical aberrant regions.

References

Aug 1, 1991·The Journal of Cell Biology·I BraakmanA Helenius
Nov 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·T R FuerstB Moss
Jan 1, 1985·Annual Review of Biochemistry·R Kornfeld, S Kornfeld
Dec 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·T C Huffaker, P W Robbins
Jul 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·W ChenA Helenius
Feb 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·C HammondA Helenius
Feb 26, 1998·Cell·B Bukau, A L Horwich
Dec 3, 1999·Science·L EllgaardA Helenius
Mar 22, 2000·The Journal of Cell Biology·E S Trombetta, A Helenius
Nov 9, 2000·The Journal of Biological Chemistry·A UjvariD N Hebert
Sep 6, 2001·Proceedings of the National Academy of Sciences of the United States of America·C ZuberJ Roth
Dec 5, 2002·The Journal of Biological Chemistry·Mili KapoorAvadhesha Surolia
Jan 9, 2003·Proceedings of the National Academy of Sciences of the United States of America·Julio J CarameloArmando J Parodi
Jan 22, 2003·Molecular Cell·Robert DanielsDaniel N Hebert
May 2, 2003·The Journal of Biological Chemistry·Edwin FrancisDaniel N Hebert
Oct 23, 2003·Annual Review of Cell and Developmental Biology·E Sergio Trombetta, Armando J Parodi
Jun 11, 2004·Annual Review of Biochemistry·Ari Helenius, Markus Aebi
Aug 21, 2004·The Journal of Biological Chemistry·Julio J CarameloArmando J Parodi
Feb 8, 2005·Nature Structural & Molecular Biology·M Claudia MaggioniIneke Braakman
Mar 5, 2005·The Journal of Biological Chemistry·Natasha KeithJulio J Caramelo

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Citations

Oct 14, 2008·The Journal of Biological Chemistry·Ning WangDaniel N Hebert
Jul 18, 2008·Molecular Biology of the Cell·Omar VanoniMaurizio Molinari
Oct 18, 2014·Nature Chemical Biology·Daniel N HebertJeffery W Kelly
Jun 18, 2010·Molecular Membrane Biology·Taku TamuraDaniel N Hebert
May 26, 2010·The Journal of Cell Biology·Bradley R PearseDaniel N Hebert
Aug 28, 2012·Trends in Biochemical Sciences·Daniel N Hebert, Maurizio Molinari
Mar 30, 2010·Seminars in Cell & Developmental Biology·Pekka MäättänenDavid Y Thomas
Dec 23, 2009·Seminars in Cell & Developmental Biology·Daniel N HebertMaurizio Molinari
Jan 5, 2010·Seminars in Cell & Developmental Biology·Cecilia D'AlessioArmando J Parodi
Oct 12, 2010·Molecular and Biochemical Parasitology·Carlos A LabriolaJulio J Caramelo
Oct 27, 2009·Trends in Biochemical Sciences·Markus AebiMaurizio Molinari
Oct 23, 2010·Molecular Cell·Alexander BuchbergerThomas Sommer
Nov 7, 2009·Biochimica Et Biophysica Acta·Bradley R Pearse, Daniel N Hebert
Mar 24, 2018·Annual Review of Plant Biology·Richard Strasser
Nov 26, 2015·Endocrine Reviews·Bruno Di Jeso, Peter Arvan
Nov 2, 2017·Current Protocols in Protein Science·Ineke BraakmanDaniel N Hebert
Oct 31, 2019·The Journal of Biological Chemistry·Benjamin M AdamsDaniel N Hebert
Apr 21, 2019·The Protein Journal·Benjamin M AdamsDaniel N Hebert
Nov 12, 2013·Journal of Cell Science·Dirk Schmidt-ArrasStefan Rose-John

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Methods Mentioned

BETA
glycosylation
pulldown
immunoprecipitation
pulldowns
electron microscopy
in vitro transcription
FCS
immunoprecipitations

Software Mentioned

BioMax

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