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Vol. 15, Issue 2, 563-574, February 2004
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F508 CFTR Pool in the Endoplasmic Reticulum Is Increased by Calnexin Overexpression
* Department of Molecular Medicine, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan;
Department of Pathology, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan; and
Department of Cell Science, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan
Submitted June 9, 2003;
Revised September 9, 2003;
Accepted October 3, 2003
Monitoring Editor: Randy Schekman
The most common cystic fibrosis transmembrane conductance regulator (CFTR) mutant in cystic fibrosis patients, 
F508 CFTR, is retained in the endoplasmic reticulum (ER) and is consequently degraded by the ubiquitin-proteasome pathway known as ER-associated degradation (ERAD). Because the prolonged interaction of F508 CFTR with calnexin, an ER chaperone, results in the ERAD of F508 CFTR, calnexin seems to lead it to the ERAD pathway. However, the role of calnexin in the ERAD is controversial. In this study, we found that calnexin overexpression partially attenuated the ERAD of F508 CFTR. We observed the formation of concentric membranous bodies in the ER upon calnexin overexpression and that the F508 CFTR but not the wild-type CFTR was retained in the concentric membranous bodies. Furthermore, we observed that calnexin overexpression moderately inhibited the formation of aggresomes accumulating the ubiquitinated F508 CFTR. These findings suggest that the overexpression of calnexin may be able to create a pool of F508 CFTR in the ER.
Abbreviations used: CF, cystic fibrosis; CFTR, cystic fibrosis transmembrane conductance regulator; ER, endoplasmic reticulum; ERAD, endoplasmic reticulum-associated degradation; IB, inclusion body; CM body, concentric membranous body.
Corresponding author. E-mail address: hirokai{at}gpo.kumamotou.ac.jp.
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