Article

The use of calnexin and calreticulin by cellular and viral glycoproteins

Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland.
Journal of Biological Chemistry (Impact Factor: 4.6). 09/2005; 280(31):28265-71. DOI: 10.1074/jbc.M501020200
Source: PubMed

ABSTRACT Calnexin and calreticulin are homologous lectin chaperones that assist maturation of cellular and viral glycoproteins in the mammalian endoplasmic reticulum. Calnexin and calreticulin share the same specificity for monoglucosylated protein-bound N-glycans but associate with a distinct set of newly synthesized polypeptides. We report here that most calnexin substrates do not associate with calreticulin even upon selective calnexin inactivation, while BiP associates more abundantly with nascent polypeptides under these conditions. Calreticulin associated more abundantly with orphan calnexin substrates only in infected cells and preferentially with polypeptides of viral origin, showing stronger dependence of model viral glycoproteins on endoplasmic reticulum lectins. This may explain why inactivation of the calnexin cycle affects viral replication and infectivity but not viability of mammalian cells.

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    • "However, they differ with respect to several features: Cnx is a transmembrane protein and has a short cytoplasmic C-terminus and ER luminal N and P domains , whereas Crt is a soluble ER luminal protein with a large capacity for Ca 2+ binding in the C-terminus. Despite their similar structures and overlapping properties they seem to complement each other in the folding of other proteins, in particular the folding of MHC I [4] [5] [6] [7]. Moreover, they seem to be able to substitute for each other in many respects [8] [9]. "
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    • "BiP is one of multiple chaperone systems important for ER quality control [25]. Calnexin and calreticulin are lectin-like chaperones that interact with glycosylated proteins and are important for viral glycoprotein processing and maturation [26]. Since DENV E is a glycoprotein, we examined its interaction with calnexin and calreticulin. "
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    • "Rather, it substantially inhibits the glucosidase II-operated de-glucosylation of labeled glycoproteins , which is required for their efficient release from calnexin (Hebert et al., 1995). We anticipated that this treatment would substantially decrease secretion of those mutants that associate with calnexin during maturation (please note that soluble variants of BACE do not associate with calreticulin; Pieren et al., 2005 and unpublished data). Cells were pulsed with radioactivity as described above and were chased for 5 min to allow BACEs association with calnexin. "
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