Lectin-deficient calreticulin retains full functionality as a chaperone for class I histocompatibility molecules

Ireland, Breanna S., Brockmeier, Ulf, Howe, Christopher M., Elliott, Tim and Williams, David B. (2008) Lectin-deficient calreticulin retains full functionality as a chaperone for class I histocompatibility molecules Molecular Biology of the Cell, 19, (6), pp. 2413-2423. (doi:10.1091/mbc.E07-10-1055). (PMID:18337472).


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Calreticulin is a molecular chaperone of the endoplasmic reticulum that uses both a lectin site specific for Glc1Man5-9GlcNAc2 oligosaccharides and a polypeptide binding site to interact with nascent glycoproteins. The latter mode of substrate recognition is controversial. To examine the relevance of polypeptide binding to protein folding in living cells, we prepared lectin-deficient mutants of calreticulin and examined their abilities to support the assembly and quality control of mouse class I histocompatibility molecules. In cells lacking calreticulin, class I molecules exhibit inefficient loading of peptide ligands, reduced cell surface expression and aberrantly rapid export from the endoplasmic reticulum. Remarkably, expression of calreticulin mutants that are completely devoid of lectin function fully complemented all of the class I biosynthetic defects. We conclude that calreticulin can use nonlectin-based modes of substrate interaction to effect its chaperone and quality control functions on class I molecules in living cells. Furthermore, pulse-chase coimmunoisolation experiments revealed that lectin-deficient calreticulin bound to a similar spectrum of client proteins as wild-type calreticulin and dissociated with similar kinetics, suggesting that lectin-independent interactions are commonplace in cells and that they seem to be regulated during client protein maturation.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1091/mbc.E07-10-1055
ISSNs: 1059-1524 (print)
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Q Science > QR Microbiology
ePrint ID: 80126
Date :
Date Event
12 March 2008e-pub ahead of print
1 June 2008Published
Date Deposited: 24 Mar 2010
Last Modified: 18 Apr 2017 20:11
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/80126

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