Role of calnexin in the ER quality control and productive folding of CFrR;: differential effect of calnexin knockout on wild-type and ΔF508 CFTR

被引：28

作者：

Okiyoneda, Tsukasa ^{[1
]}

Niibori, Akiko ^{[1
]}

Harada, Kazutsune ^{[1
]}

Kohno, Taijun ^{[1
]}

Michalak, Marek ^{[2
]}

Duszyk, Marek ^{[3
]}

Wada, Ikuo ^{[4
]}

Ikawa, Masahito ^{[5
]}

Shuto, Tsuyoshi ^{[1
]}

Suico, Mary Ann ^{[1
]}

Kai, Hirofumi ^{[1
]}

机构：

[1] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Mol Med, Global COE Cell Fate Regulat Res & Educ Unit, Kumamoto 8620973, Japan

[2] Univ Alberta, Dept Biochem, Edmonton, AB T6G 2H7, Canada

[3] Univ Alberta, Med Res Council Grp Mol Biol Membranes, Dept Physiol, Edmonton, AB T6G 2H7, Canada

[4] Fukushima Med Univ, Sch Med, Inst Biomed Sci, Dept Cell Sci, Fukushima 9601295, Japan

[5] Osaka Univ, Genome Informat Res Ctr, Suita, Osaka 5650871, Japan

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2008年 / 1783卷 / 09期

关键词：

calnexin; calnexin knockout; CFTR; ER quality control;

D O I：

10.1016/j.bbamcr.2008.04.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cystic fibrosis (CF) is caused by the mutation in CF transmembrane conductance regulator (CFTR), a cAMP-dependent Cl- channel at the plasma membrane of epithelium. The most common mutant, Delta F508 CFTR, has competent Cl- channel function, but fails to express at the plasma membrane since it is retained in the endoplasmic reticulum (ER) by the ER quality control system. Here, we show that calnexin (CNX) is not necessary for the ER retention of Delta F508 CFTR. Our data show that CNX knockout (KO) does not affect the biosynthetic processing, cellular localization or the Cl- channel function of Delta F508 CFTR. Importantly, cAMP induced Cl- current in colonic epithelium from CNX KO/Delta F508 CFFR mice was comparable with that of Delta F508 CFFR mice, indicating that CNX KO failed to rescue the ER retention of Delta F508 CFTR in vivo. Moreover, we show that CNX assures the efficient expression of WT CFFR, but not Delta F508 CFTR, by inhibiting the proteasomal degradation, indicating that CNX might stimulate the productive folding of WT CFFR, but not Delta F508 CFTR, which has folding defects. (c) 2008 Elsevier B.V. All rights reserved.

引用

页码：1585 / 1594

页数：10