Calnexin

2018 Proposed


Calnexin is a trans-memembrane lectin and chaperone for glycoproteins with a molecular weight of 64-66 kDa (Tatu, U. and Helenius, A., Interactions between newly synthesized glycoproteins, calnexin and a network of resident chaperones in the endoplasmic reticulum, J.Cell Biol. 136, 555-565, 1997; Yamashita, T., Kiyoki, E., Tomita, Y., and Taira, H., Immunoaffinity purification and identification of the molecular chaperone calnexin, Biosci.Biotechnol.Biochem. 63, 1491-1493, 1999; Lamriben, L., Graham, J.B., Adams, B.M., and Herbert, D.N., N-Glycan-based ER molecular chaperone and protein quality control system: The calnexin binding cycle, Traffic 17, 306-326. 2016). Calnexin was originally described as p88, a 88 kDa protein, which was transiently associated with class I histocompatibity heavy chain in murine tumor cell lines (Degen, E. and Williams, D.B., Participation of a novel 88-kD protein in the biogenesis of murine class I histocompatibility molecules, J.Cell Biol.  112, 1099-1115, 1991)  p88 protein was subsequently shown to be identical with calnexin (Ahluwalia, N., Bergeron, J.J., Wada, I., Degen, E., and Williams, E.B., The p88 molecular chaperone is identical to the endoplasmic reticulum membrane protein, calnexin, J.Biol.Chem. 267, 10914-10918, 1992).  Calnexin was shown to have homology with calreticulin (Bergeron, J.J.M., Brenner, M.B., Thomas, D.Y., and Willams, D.B., Calnexin: a membrane-based chaperone of the endoplasmic reticulum, Trends Biochem.Sci. 19, 124-129, 1994) and participates with calreticulin as a chaperone to maintain glycoprotein quality in export from the ER(endoplasmic reticulum)(Wiliams ,D.B., Beyond lectins: the calnexin/calreticulin chaperone system of the endoplasmic reticulum, J.Cell.Sci. 119, 615-523, 2006). Calnexin (and calreticulin) are described as lectins on the basis of their abilty to bind to glycoproteins (Hammond, C., Braakman, I., and Helenius, A., Role of N-linked oligosaccharide recognition, glucose timming, and calnexin in glycoprotein folding and quality control, Proc.Natl.Acad.Sci. USA 91, 913-917, 1994;  Bergeron, J.J. Zapun, A., Ou, W.J., et al., The role of the lectin calnexin in conformation independent binding to N-linked glycoproteins and quality control, Adv.Exp.Biol.Med. 435, 105-116, 1998; Hirano, M., Imagawa, A., and Totani, K., Stratified analysis of lectin-like chaperones in the folding disease-related metabolic syndrome rat model, Biochem.Biophys.Res.Commun. 478, 247-253, 2016). Calnexin also recruits processing enzymes such as protein disulfide isomerase (Nakao,H., Seko,A., Ito, Y., and Sakono, M., PDI family protein ERp29 recognizes P-domain of molecular chaperone calnexin, Biochem.Biophys.Res.Commun. 487, 763-767, 2017; Kozlov, G., Muñoz-Excobar, J., Castro,K., and Gehring, K., Mapping the ER interactome: The P domains of calnexin and calreticulin as plurivalent adaptors for foldases and chaperones, Structure 25, 1415-1422, 2017).  Palmitoylation of calnexin serve to regulate the function of calnexin; palmitoylation shifts calnexin to calcium regulation while a decrease in palmitoylation shifts  calnexin function to the better know chaperone function (Lynes, E.M., Raturi, A., Shenkman, M., et al., Palmitoylation is the switch that assigns calnexin to quality control or ER Ca2+signaling, J.Cell Sci. 126, 3893-3903, 2013).  The function of calnexin is also regulated by phosphorylation (Chevet,  E., Smirle, J., Cameron, P.H., et al., Calnexin phosphorylation: linking cytoplastmic signallying to endoplasmic reticulum luminal functions. Semin.Cell Dev.Biol. 21, 486-490, 2010; Bollo,M., Paredex, R.M., Holstein, D., et al., Calcineurin interacts with PERK and dephosphorylates calnexin to relieve ER stress in mammals and frogs, PLoS One 5(8):e11925, 2010; Dallavilla,T., Abrami, L., Sandoz, P.A., et al., Model-driven understanding of palmitoylation dynamics: Regulated acylation of the endoplasmic reticulum chaperone calnexin, PLoS Comput.Biol. 12(2):e1004774, 2016)

2007 published

A lectin protein associated with the endoplasmic reticulum which functions as a chaperone. See Cresswell, P., Androlewicz, M.J. and Ortmann, B., Assembly and transport of class I MHC-peptide complexes, Ciba Found.Symp. 187, 150-162, 1994; Bergeron, J.J., Brenner, M.B., Thomas, D.Y., and Williams, D.B., Calnexin: a membrane-bound chaperone or the endoplasmic reticulum, Trends Biochem.Sci. 19, 124-128, 1995;, Parham, P., Functions for MHC class I carbohydrates inside and outside the cell, Trends Biochem.Sci. 21, 472-433, 1996; Trombetta, E.S. and Helenius, A., Lectins as chaperones in glycoprotein folding, Curr.Opin.Struct.Biol. 8, 587-592, 1998; Huari, H.. Appenzeller, C., Kuhn, F., and Nufer, O., Lectins and traffic in the secretory pathway, FEBS Lett. 476, 32-37, 2000; Ellgaard, L. and Frickel, E.M., Calnexin, calreticulin, and ERp57: teammates in glycoprotein folding, Cell.Biochem.Biophys. 39, 223-247, 2003; Spiro, R.G., Role of N-linked polymannose oligosaccharides in targeting glycoproteins for endoplasmic reticulum-associated degradation, Cell.Mol.Life Sci. 61, 1025-1041, 2004; Bedard, K., Szabo, E., Michalak, M., and Opas, M., Cellular functions of endoplasmic reticulum chaperones calreticulin, calnexin, and ERp57, Int.Rev.Cytol. 245, 91-121, 2005; Ito, Y., Hagihara, S., Matsuo, I., and Totani, K., Structural approaches to the study of oligosaccharides in glycoprotein quality control, Curr.Opin.Struct.Biol.15, 481-489, 2005.