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アクティブボード・２００２年 ８月
研究発表を行った学会；第５５回日本細胞生物学会大会
２００２年５月２１日～２３日（横浜）
タイトル；Calnexin attenuates the ER-associated degradation of immature CFTR
発表者；沖米田 司 氏
（大学院 薬学研究科 遺伝子機能応用学（薬理学）講座）
Abstract；
Cystic fibrosis (CF) is caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR), which functions as a cAMP-dependent Cl- channel on the plasma membrane. △F508 CFTR, the most common CFTR mutant in CF patients, is retained in the ER and degraded by ER-associated degradation (ERAD). Although an ER chaperone calnexin has been thought to be involved in the CFTR biogenesis, the role of calnexin in ERAD is unclear. Here, we examine whether calnexin targets △F508 CFTR to the ERAD or calnexin prevents it from the ERAD. When calnexin was overexpressed, the ERAD of both wt and △F508 CFTR was attenuated. Immunocytochemical analyses showed that calnexin overexpression induced the formation of inclusion body (IB)-like structures where calnexin and △F508 CFTR accumulated. The IB-like structures were detergent-soluble and were not co-localized with ubiquitinated proteins, suggesting that they are not aggresomes. The IB-like structures were localized in the ER, suggesting that △F508 CFTR stabilized by calnexin accumulates in the ER. Interestingly, upon inhibition of the ER-Golgi transport, wt CFTR was also localized in the IB-like structures by calnexin overexpression, suggesting that calnexin interacts with the ER-localized CFTR to inhibit the ERAD. These results indicate that calnexin may prevent the ERAD of CFTR that could not be recognized with the ER export machinery.
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