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首页> 外文期刊>Molecular and Cellular Biology >Plasma Membrane CFTR Regulates RANTES Expression via Its C-Terminal PDZ-Interacting Motif
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Plasma Membrane CFTR Regulates RANTES Expression via Its C-Terminal PDZ-Interacting Motif

机译：血浆膜CFTR通过其C末端PDZ相互作用基元调节RANTES表达。

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Despite the identification of 1,000 mutations in the cystic fibrosis gene product CFTR, there remains discordance between CFTR genotype and lung disease phenotype. The study of CFTR, therefore, has expanded beyond its chloride channel activity into other possible functions, such as its role as a regulator of gene expression. Findings indicate that CFTR plays a role in the expression of RANTES in airway epithelia. RANTES is a chemokine that has been implicated in the regulation of mucosal immunity and the pathogenesis of airway inflammatory diseases. Results demonstrate that CFTR triggers RANTES expression via a mechanism that is independent of CFTR's chloride channel activity. Neither pharmacological inhibition of CFTR nor activation of alternative chloride channels, including hClC-2, modulated RANTES expression. Through the use of CFTR disease-associated and truncation mutants, experiments suggest that CFTR-mediated transcription factor activation and RANTES expression require (i) insertion of CFTR into the plasma membrane and (ii) an intact CFTR C-terminal PDZ-interacting domain. Expression of constructs encoding wild-type or dominant-negative forms of the PDZ-binding protein EBP50 suggests that EBP50 may be involved in CFTR-dependent RANTES expression. Together, these data suggest that CFTR modulates gene expression in airway epithelial cells while located in a macromolecular signaling complex at the plasma membrane.
机译：尽管在囊性纤维化基因产物CFTR中鉴定出1,000个突变，但CFTR基因型和肺部疾病表型之间仍然存在矛盾。因此，CFTR的研究已从其氯离子通道活性扩展到其他可能的功能，例如其作为基因表达调节剂的作用。研究结果表明CFTR在气道上皮中RANTES的表达中起作用。 RANTES是一种趋化因子，参与了粘膜免疫的调节和气道炎性疾病的发病机制。结果表明，CFTR通过独立于CFTR氯离子通道活性的机制触发RANTES表达。 CFTR的药理抑制作用或其他氯通道（包括hClC-2）的激活均不能调节RANTES表达。通过使用与CFTR疾病相关和截短的突变体，实验表明CFTR介导的转录因子激活和RANTES表达需要（i）将CFTR插入质膜和（ii）完整的CFTR C端PDZ相互作用域。编码野生型或显性负型PDZ结合蛋白EBP50的构建体的表达表明EBP50可能参与CFTR依赖的RANTES表达。在一起，这些数据表明CFTR调节气道上皮细胞中的基因表达，同时位于质膜的大分子信号复合物中。

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