The epithelial sodium channel, ENaC, located at the apical membrane in many epithelia, is the rate-limiting step for sodium reabsorption. Tight regulation of the plasma membrane population of ENaC is required as hyper- or hypotension may result if too many or too few ENaCs are present. Endocytosed ENaC travels to the early endosome and is then either trafficked to the lysosome for degradation or recycled back to the plasma membrane. Recently, the retromer recycling complex, located at the early endosome, has been implicated in plasma membrane protein recycling pathways. We hypothesized that retromer is required for recycling of ENaC. Stabilization of retromer function with the retromer stabilizing chaperone R55 increased ENaC current, while knockdown or overexpression of individual retromer and associated proteins altered ENaC current and cell surface population of ENaC. KIBRA was identified as an ENaC binding protein allowing ENaC to link to Snx4 to alter ENaC trafficking. Knockdown of the retromer-associated cargo-binding Snx27 protein did not alter ENaC current, whereas CCDC22, a CCC-complex protein, coimmunoprecipitated with ENaC and CCDC22 knockdown decreased ENaC current and population at the cell surface. Together our results confirm that retromer and the CCC complex play a role in recycling of ENaC to the plasma membrane.

中文翻译：

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Retromer参与上皮钠通道运输

位于许多上皮细胞顶膜的上皮钠通道ENaC是钠重吸收的限速步骤。需要严格调节ENaC的质膜数量，因为如果存在过多或过少的ENaC，可能会导致高血压或低血压。内吞的ENaC到达早期的内体，然后被转运到溶酶体进行降解，或者被循环回质膜。最近，位于早期内体的逆转录酶回收复合物与质膜蛋白回收途径有关。我们假设ENaC的回收需要翻新机。用稳定剂伴侣伴侣R55稳定稳定剂功能可增加ENaC电流，而敲除或个别逆转录酶及相关蛋白的过表达改变了ENaC电流和ENaC的细胞表面种群。KIBRA被鉴定为一种ENaC结合蛋白，可使ENaC与Snx4连接以改变ENaC的运输。敲除与remeromer相关的与货物结合的Snx27蛋白不会改变ENaC电流，而CCDC22是一种CCC复合蛋白，与ENaC和CCDC22敲低免疫共沉淀，可降低ENaC电流和细胞表面的细胞数量。我们的研究结果共同证明，resterer和CCC配合物在ENaC回收到质膜中发挥了作用。与ENaC和CCDC22组合免疫共沉淀的CCC复合蛋白减少了ENaC电流和细胞表面的种群。我们的研究结果共同证明，resteromer和CCC配合物在ENaC回收到质膜中发挥了作用。与ENaC和CCDC22组合免疫共沉淀的CCC复合蛋白减少了ENaC电流和细胞表面的种群。我们的研究结果共同证明，resterer和CCC配合物在ENaC回收到质膜中发挥了作用。