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Calreticulin Controls the Rate of Assembly of CD1d Molecules in the Endoplasmic Reticulum

CD1d is an MHC class I-like molecule comprised of a transmembrane glycoprotein (heavy chain) associated with β(2)-microglobulin (β(2)m) that presents lipid antigens to NKT cells. Initial folding of the heavy chain involves its glycan-dependent association with calreticulin (CRT), calnexin (CNX), and...

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Autores principales: Zhu, Yajuan, Zhang, Wei, Veerapen, Natacha, Besra, Gurdyal, Cresswell, Peter
Formato: Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2992262/
https://www.ncbi.nlm.nih.gov/pubmed/20861015
http://dx.doi.org/10.1074/jbc.M110.170530
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author Zhu, Yajuan
Zhang, Wei
Veerapen, Natacha
Besra, Gurdyal
Cresswell, Peter
author_facet Zhu, Yajuan
Zhang, Wei
Veerapen, Natacha
Besra, Gurdyal
Cresswell, Peter
author_sort Zhu, Yajuan
collection PubMed
description CD1d is an MHC class I-like molecule comprised of a transmembrane glycoprotein (heavy chain) associated with β(2)-microglobulin (β(2)m) that presents lipid antigens to NKT cells. Initial folding of the heavy chain involves its glycan-dependent association with calreticulin (CRT), calnexin (CNX), and the thiol oxidoreductase ERp57, and is followed by assembly with β(2)m to form the heterodimer. Here we show that in CRT-deficient cells CD1d heavy chains convert to β(2)m-associated dimers at an accelerated rate, indicating faster folding of the heavy chain, while the rate of intracellular transport after assembly is unaffected. Unlike the situation with MHC class I molecules, antigen presentation by CD1d is not impaired in the absence of CRT. Instead, there are elevated levels of stable and functional CD1d on the surface of CRT-deficient cells. Association of the heavy chains with the ER chaperones Grp94 and Bip is observed in the absence of CRT, and these may replace CRT in mediating CD1d folding and assembly. ER retention of free CD1d heavy chains is impaired in CRT-deficient cells, allowing their escape and subsequent expression on the plasma membrane. However, these free heavy chains are rapidly internalized and degraded in lysosomes, indicating that β(2)m association is required for the exceptional resistance of CD1d to lysosomal degradation that is normally observed.
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spelling pubmed-29922622011-12-03 Calreticulin Controls the Rate of Assembly of CD1d Molecules in the Endoplasmic Reticulum Zhu, Yajuan Zhang, Wei Veerapen, Natacha Besra, Gurdyal Cresswell, Peter J Biol Chem Immunology CD1d is an MHC class I-like molecule comprised of a transmembrane glycoprotein (heavy chain) associated with β(2)-microglobulin (β(2)m) that presents lipid antigens to NKT cells. Initial folding of the heavy chain involves its glycan-dependent association with calreticulin (CRT), calnexin (CNX), and the thiol oxidoreductase ERp57, and is followed by assembly with β(2)m to form the heterodimer. Here we show that in CRT-deficient cells CD1d heavy chains convert to β(2)m-associated dimers at an accelerated rate, indicating faster folding of the heavy chain, while the rate of intracellular transport after assembly is unaffected. Unlike the situation with MHC class I molecules, antigen presentation by CD1d is not impaired in the absence of CRT. Instead, there are elevated levels of stable and functional CD1d on the surface of CRT-deficient cells. Association of the heavy chains with the ER chaperones Grp94 and Bip is observed in the absence of CRT, and these may replace CRT in mediating CD1d folding and assembly. ER retention of free CD1d heavy chains is impaired in CRT-deficient cells, allowing their escape and subsequent expression on the plasma membrane. However, these free heavy chains are rapidly internalized and degraded in lysosomes, indicating that β(2)m association is required for the exceptional resistance of CD1d to lysosomal degradation that is normally observed. American Society for Biochemistry and Molecular Biology 2010-12-03 2010-09-22 /pmc/articles/PMC2992262/ /pubmed/20861015 http://dx.doi.org/10.1074/jbc.M110.170530 Text en © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles
spellingShingle Immunology
Zhu, Yajuan
Zhang, Wei
Veerapen, Natacha
Besra, Gurdyal
Cresswell, Peter
Calreticulin Controls the Rate of Assembly of CD1d Molecules in the Endoplasmic Reticulum
title Calreticulin Controls the Rate of Assembly of CD1d Molecules in the Endoplasmic Reticulum
title_full Calreticulin Controls the Rate of Assembly of CD1d Molecules in the Endoplasmic Reticulum
title_fullStr Calreticulin Controls the Rate of Assembly of CD1d Molecules in the Endoplasmic Reticulum
title_full_unstemmed Calreticulin Controls the Rate of Assembly of CD1d Molecules in the Endoplasmic Reticulum
title_short Calreticulin Controls the Rate of Assembly of CD1d Molecules in the Endoplasmic Reticulum
title_sort calreticulin controls the rate of assembly of cd1d molecules in the endoplasmic reticulum
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2992262/
https://www.ncbi.nlm.nih.gov/pubmed/20861015
http://dx.doi.org/10.1074/jbc.M110.170530
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