PDZ binding motif-dependent localization of K+ channel on the basolateral side in distal tubules
PDZ binding motif-dependent localization of K+ channel on the basolateral side in distal tubules
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DOI：
10.1152/ajprenal.00203.2004
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发表时间：
2004-12-01
影响因子：
4.2
通讯作者：
Ito, S
中科院分区：
文献类型：
--
作者：
Tanemoto, M;Abe, T;Ito, S
Kir5.1本身是一种无功能的内向整流钾通道，可与其他蛋白组装形成功能性通道。我们先前表明Kir5.1与Kir4.1组装并在肾脏中起酸碱调节剂的作用。在这项研究中，我们研究了Kir5.1在肾内的分布，通过RT-PCR分析解剖肾单位节段和免疫组化分析与特异性抗Kir5.1抗体。Kir5.1在远曲小管中表达较强，在Henle袢升支粗段中表达较弱。Kir5.1与Kir4.1的共定位表明Kir5.1/Kir4.1异聚体在这些肾单位节段中表达。在肾上皮细胞系Madin-Darby犬肾细胞中，Kir4.1异聚体的形成改变了Kir5.1从细胞内组分到细胞表面的定位。包括Kir4.1的PDZ结合基序的COOH末端细胞质部分负责这种细胞内定位。这些数据表明Kir4.1的COOH末端上的信号，包括PDZ结合基序，决定了Kir5.1/Kir4.1异聚体在远端小管中的细胞内定位。
Kir5.1, a nonfunctional inwardly rectifying K+ channel by itself, can form functional channels by assembling with other proteins. We previously showed that Kir5.1 assembled with Kir4.1 and functioned as an acid-base regulator in the kidney. In this study, we examined the intrarenal distribution of Kir5.1 by RT-PCR analysis on dissected nephron segments and immunohistochemical analysis with the specific anti-Kir5.1 antibody. Strong expression of Kir5.1 was detected in distal convoluted tubules, and weak expression was also detected in thick ascending limb of Henle's loop. Colocalization of Kir5.1 with Kir4.1 indicated expression of Kir5.1/Kir4.1 heteromer in these nephron segments. In a renal epithelial cell line, Madin-Darby canine kidney cells, heteromer formation with Kir4.1 changed the localization of Kir5.1 from intracellular components to the cell surface. The COOH-terminal cytoplasmic portion that includes the PDZ binding motif of Kir4.1 was responsible for this intracellular localization. These data suggest the signals on the COOH terminus of Kir4.1, including PDZ binding motif, determine the intracellular localization of Kir5.1/Kir4.1 heteromer in distal tubules.