2010/09/23 by Yajuan Zhu, Wei Zhang, Natacha Veerapen +2 · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · Immunology and Microbiology · Medicine · #Biology #Calreticulin #Cell biology #Chemistry #Endoplasmic Reticulum Stress and Disease #Endoplasmic reticulum #Immune Cell Function and Interaction #Pancreatic function and diabetes #STIM1
paper · pdf · doi:10.1074/jbc.m110.170530
openalex publication_date 2010/09/23 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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.