Bafilomycin Al-sensitive pathway is required for the maturation of cystic fibrosis transmembrane conductance regulator
Bafilomycin Al-sensitive pathway is required for the maturation of cystic fibrosis transmembrane conductance regulator
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DOI：
10.1016/j.bbamcr.2006.08.032
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发表时间：
2006-10-01
影响因子：
5.1
通讯作者：
Kai, Hirofumi
中科院分区：
文献类型：
--
作者：
Okiyoneda, Tsukasa;Nilbori, Akiko;Kai, Hirofumi
囊性纤维化（CF）是白种人中最常见的致死性遗传性疾病，其由CIF跨膜传导调节因子（CFTR）的运输缺陷引起，CIF跨膜传导调节因子是质膜上cAMP依赖性Cl-通道。CFTR的运输途径被认为是非常规的，因为CFTR的成熟受到syntaxin 13功能障碍的抑制，syntaxin 13参与通过内体途径的蛋白质再循环。在这项研究中，为了阐明CFTR成熟是否需要内体运输，我们利用了一种特异性的液泡H+-ATP酶抑制剂，巴弗洛霉素At（BafA 1），它抑制早期内体的蛋白运输。我们的数据表明，低浓度的BafA 1（50 nM）降低了成熟CFTR的表达，但诱导未成熟CFTR在含有早期核内体标记物的近核区域的积累。脉冲追踪分析表明，BafA 1抑制CFTR的成熟，但它稍微稳定未成熟的CFTR。这些结果表明，BafA 1敏感途径是CFTR成熟所必需的，并强调内体运输途径可能参与CFTR的成熟。(c)2006 Elsevier B. V.保留所有权利。
Cystic fibrosis (CF) is the most common lethal genetic disease in Caucasians caused by the trafficking defects of CIF transmembrane conductance regulator (CFTR), which is a cAMP-dependent Cl- channel at the plasma membrane. The trafficking pathway of CFTR is thought to be non-conventional because CFTR maturation is inhibited by the dysfunction of syntaxin 13, which is involved in protein recycling via endosomal pathway. In this study, to clarify whether the endosomal trafficking is required for CFTR maturation, we utilized a specific vacuolar H+-ATPase inhibitor, bafilomycin At (BafA1), which inhibits the protein trafficking from early endosome. Our data showed that low concentration of BafA1 (50 nM) decreased the expression of mature CFTR but induced the accumulation of immature CFTR in the juxta-nuclear region containing an early endosome marker. Pulse-chase analysis showed that BafA1 inhibited the maturation of CFTR, but it slightly stabilized immature CFTR. These results indicate that BafA1-sensitive pathway is required for CFTR maturation and emphasize that endosomal trafficking pathway might be involved in the maturation of CFTR. (c) 2006 Elsevier B.V. All rights reserved.