Delta F508 CFTR pool in the endoplasmic reticulum is increased by calnexin overexpression.
The most common cystic fibrosis transmembrane conductance regulator (CFTR) mutant in cystic fibrosis patients, Delta 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 Delta F508 CFTR with calnexin, an ER chaperone, results in the ERAD of Delta 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 Delta F508 CFTR. We observed the formation of concentric membranous bodies in the ER upon calnexin overexpression and that the Delta 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 Delta F508 CFTR. These findings suggest that the overexpression of calnexin may be able to create a pool of Delta F508 CFTR in the ER.
Okiyoneda
Tsukasa
T
Department of Molecular Medicine, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Harada
Kazutsune
K
Takeya
Motohiro
M
Yamahira
Kaori
K
Wada
Ikuo
I
Shuto
Tsuyoshi
T
Suico
Mary Ann
MA
Hashimoto
Yasuaki
Y
Kai
Hirofumi
H
D000818:Animals; D016466:CHO Cells; D037281:Calnexin / Q000378:metabolism*; D002451:Cell Compartmentation / Q000502:physiology*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009154:Mutation; D034741:RNA, Small Interfering / Q000235:genetics; D014452:Ubiquitins / Q000378:metabolism*
D034741:RNA, Small Interfering; D014452:Ubiquitins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D037281:Calnexin