Non-conventional trafficking of the cystic fibrosis transmembrane conductance regulator through the early secretory pathway
Non-conventional trafficking of the cystic fibrosis transmembrane conductance regulator through the early secretory pathway
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DOI：
10.1074/jbc.m110263200
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发表时间：
2002-03-29
影响因子：
4.8
通讯作者：
Balch, WE
中科院分区：
文献类型：
--
作者：
Yoo, JS;Moyer, BD;Balch, WE
囊性纤维化跨膜传导调节因子（CFTR）从内质网（ER）通过高尔基体运输的机制在很大程度上是未知的，该步骤在患有导致囊性纤维化的流行CFTR-DeltaF 508突变的个体中受损。最近的形态学观察表明，CFTR在很大程度上不存在于原位高尔基体中（Bannykh，S.一、班内赫湾L，鱼，K。N.，莫耶，B。D、赖尔登，J.R.，Balch，W. E.（2000）Traffic 1，852-870），提高了通过早期分泌途径的新型运输途径的可能性。我们现在报告说，出口的CFTR从ER是由传统的外壳蛋白复合物II（COPII）在所有测试的细胞类型。值得注意的是，以细胞类型特异性的方式，CFTR从核心糖基化（带B）ER形式加工成复合糖基化（带Q同种型。遵循非常规途径，其对显性负性Arf 1、Rab 1a/Rab 2 GTP酶或SNAP受体（SNARE）组分突触融合蛋白5不敏感，所有这些都阻断从ER到高尔基体的常规运输途径。此外，通过非常规途径的CFTR运输被晚期内体靶向SNARE突触融合蛋白13的过表达有力地阻断，表明通过晚期高尔基体/内体系统的再循环是CFTR成熟的先决条件。我们的结论是，CFTR运输在早期分泌途径可能涉及一种新的途径之间的ER和晚期高尔基体/内体室，可能会影响CFTR的细胞表面上的极化上皮细胞的发育表达。
The mechanism(s) of cystic fibrosis transmembrane conductance regulator (CFTR) trafficking from the endoplasmic reticulum (ER) through the Golgi apparatus, the step impaired in individuals afflicted with the prevalent CFTR-DeltaF508 mutation leading to cystic fibrosis, is largely unknown. Recent morphological observations suggested that CFTR is largely absent from the Golgi in situ (Bannykh, S. I., Bannykh, G. L, Fish, K. N., Moyer, B. D., Riordan, J. R., and Balch, W. E. (2000) Traffic 1, 852-870), raising the possibility of a novel trafficking pathway through the early secretory pathway. We now report that export of CFTR from the ER is regulated by the conventional coat protein complex II (COPII) in all cell types tested. Remarkably, in a cell type-specific manner, processing of CFTR from the core-glycosylated (band B) ER form to the complex-glycosylated (band Q isoform. followed a non-conventional pathway that was insensitive to dominant negative Arf1, Rab1a/Rab2 GTPases, or the SNAP REceptor (SNARE) component syntaxin 5, all of which block the conventional trafficking pathway from the ER to the Golgi. Moreover, CFTR transport through the non-conventional pathway was potently blocked by overexpression of the late endosomal target-SNARE syntaxin 13, suggesting that recycling through a late Golgi/endosomal system was a prerequisite for CFTR maturation. We conclude that CFTR transport in the early secretory pathway can involve a novel pathway between the ER and late Golgi/endosomal compartments that may influence developmental expression of CFTR on the cell surface in polarized epithelial cells.