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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...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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American Society for Biochemistry and Molecular Biology
2010
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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. |
format | Text |
id | pubmed-2992262 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
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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