Calnexin is an abundant 90kDa chaperone protein that resides in the membrane of the endoplasmic reticulum. Calnexin and the related calreticulin protein function together to ensure the proper folding of glycoproteins. By binding to partially folded or misfolded proteins, Calnexin functions as an important quality control monitor ensuring proper folding of proteins destined for the plasma membrane or secretion. Calnexin contains a lectin site that recognizes substrate proteins through a transient and intermediate oligosaccharide containing a terminal glucose residue. Through this interaction calnexin binds to and participates in the folding of most if not all glycoproteins. Calnexin also contains binding sites for it cofactors ATP and Ca2+ and is able to recruit enzymes that catalyze disulfide bond formation and isomeriztion to aid in folding. Calnexin binding retains substrate proteins in the ER until they are fully mature and their intermediate oligosaccharide is cleaved by glucosidase II or, for terminally misfolded proteins, until they are targeted for degradation. While cells in culture can survive without calnexin, mice suffer sever neurological problems indicating roles in developmental processes beyond protein folding like regulating Ca2+ homeostasis. Given its abundance calnexin antibodies serve as an excellent marker for the endoplasmic reticulum.
In the initial characterization of calnexin, Galvin et al. used a monoclonal calnexin antibody to examine the expression of calnexin protein by western blotting 1. This study also demonstrated an association with MHC class I molecules through immunoprecipitation. This was the initial indication calnexin functions as a chaperone for MHC class I proteins. In a more recent study Park et al. used labeled calnexin antibodies in immunogold labeling for electron microscopy 2. They examined the localization of DISC1, a gene involved in schizophrenia, in relation to calnexin and investigated DISC1’s role in calcium dynamics. These studies demonstrated the importance of calnexin antibodies as tools to investigate the proteins involved in ER pathways. The first study generated a calnexin antibody to provide one of the first characterizations of the calnexin protein and its basic mechanisms. The latter study, on the other hand, studied the poorly characterized DISC1 in relation to the calnexin pathway.
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PMIDs
- 1326756
- 25732993