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A more recent version of this article appeared on February 1, 2004
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Submitted on June 9, 2003
Revised on September 9, 2003
Accepted on October 3, 2003
F508 CFTR pool in the ER is increased by calnexin overexpression
1 Departments of Molecular Medicine, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
2 Departments of Pathology, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
3 Department of Cell Science, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan/CREST, JST
* Corresponding author. E-mail address: hirokai{at}gpo.kumamoto-u.ac.jp.
The most common cystic fibrosis transmembrane conductance regulator
(CFTR) mutant in cystic fibrosis (CF) 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). Since 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 (CM bodies) in the ER upon
calnexin overexpression and that the F508 CFTR but not the wt CFTR
was retained in the CM 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.
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