Induction of HSP70 promotes ΔF508 CFTR trafficking
Induction of HSP70 promotes ΔF508 CFTR trafficking
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DOI：
10.1152/ajplung.2001.281.1.l58
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发表时间：
2001-07-01
影响因子：
4.9
通讯作者：
Zeitlin, PL
中科院分区：
文献类型：
--
作者：
Choo-Kang, LR;Zeitlin, PL
Delta F508囊性纤维化跨膜传导调节因子（CFTR）是一种温度敏感的运输突变体，在凝胶电泳中检测为未成熟的160 kDa形式（带B）。本研究的目的是检验HSP 70（70 kDa热休克蛋白家族成员）促进Delta F508 CFTR加工成成熟的180 kDa形式（条带C）的假设。采用药理学和遗传学技术诱导HSP 70。用4-苯基丁酸钠（4PBA）处理IB 3 -1细胞以促进Delta F508 CFTR成熟为带C。观察到C带和总细胞HSP 70的剂量依赖性增加。在这些条件下，HSP 70-CFTR复合物增加，70-kDa热休克同源蛋白-CFTR复合物减少。在用HSP 70表达质粒转染并暴露于谷氨酰胺（HSP 70的诱导剂）后，也观察到Delta F508 CFTR成熟增加。用免疫荧光技术，CFTR带C的出现增加与CFTR分布超出核周区域相关。这些数据表明，HSP 70的诱导促进Delta F508 CFTR成熟和运输。
The Delta F508 cystic fibrosis transmembrane conductance regulator (CFTR) is a temperature-sensitive trafficking mutant that is detected as an immature 160-kDa form (band B) in gel electrophoresis. The goal of this study was to test the hypothesis that HSP70, a member of the 70-kDa heat shock protein family, promotes Delta F508 CFTR processing to the mature 180-kDa form (band C). Both pharmacological and genetic techniques were used to induce HSP70. IB3-1 cells were treated with sodium 4-phenylbutyrate (4PBA) to promote maturation of Delta F508 CFTR to band C. A dose-dependent increase in band C and total cellular HSP70 was observed. Under these conditions, HSP70-CFTR complexes were increased and 70-kDa heat shock cognate protein-CFTR complexes were decreased. Increased Delta F508 CFTR maturation was also seen after transfection with an HSP70 expression plasmid and exposure to glutamine, an inducer of HSP70. With immunofluorescence techniques, the increased appearance of CFTR band C correlated with CFTR distribution beyond the perinuclear regions. These data suggest that induction of HSP70 promotes Delta F508 CFTR maturation and trafficking.