K+ 通道定位错误导致 EAST/SeSAME 综合征的肾性盐耗。
Mislocalization of K+ channels causes the renal salt wasting in EAST/SeSAME syndrome.
机构信息
Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 174-8605, Japan.
Division of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai 980-8575, Japan.
出版信息
FEBS Lett. 2014 Mar 18;588(6):899-905. doi: 10.1016/j.febslet.2014.02.024. Epub 2014 Feb 20.
The Kir4.1/Kir5.1 channel mediates basolateral K(+) recycling in renal distal tubules; this process is critical for Na(+) reabsorption at the tubules. Mutations in Kir4.1 are associated with EAST/SeSAME syndrome, a genetic disorder characterized by renal salt wasting. In this study, we found that MAGI-1 anchors Kir4.1 channels (Kir4.1 homomer and Kir4.1/Kir5.1 heteromer) and contributes to basolateral K(+) recycling. The Kir4.1 A167V mutation associated with EAST/SeSAME syndrome caused mistrafficking of the mutant channels and inhibited their expression on the basolateral surface of tubular cells. These findings suggest mislocalization of the Kir4.1 channels contributes to renal salt wasting.
Kir4.1/Kir5.1 通道介导肾脏远曲小管基底外侧的 K(+)再循环；这一过程对于肾小管的 Na(+)重吸收至关重要。Kir4.1 的突变与 EAST/SeSAME 综合征有关，这是一种遗传性疾病，其特征是肾脏盐耗竭。在这项研究中，我们发现 MAGI-1 锚定 Kir4.1 通道（Kir4.1 同源二聚体和 Kir4.1/Kir5.1 异源二聚体）并有助于基底外侧的 K(+)再循环。与 EAST/SeSAME 综合征相关的 Kir4.1 A167V 突变导致突变通道的错误运输，并抑制其在管状细胞基底外侧表面的表达。这些发现表明 Kir4.1 通道的定位错误导致肾脏盐耗竭。
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