Barttin increases surface expression and changes current properties of ClC-K channels
Barttin increases surface expression and changes current properties of ClC-K channels
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Barttin 增加表面表达并改变 ClC-K 通道的当前特性
DOI：
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
H. Seyberth
中科院分区：
文献类型：
--
作者：
S. Waldegger;N. Jeck;P. Barth;M. Peters;H. Vitzthum;K. Wolf;A. Kurtz;M. Konrad;H. Seyberth
抽象的。术语Bartter综合征包括一组异质性常染色体隐性失盐性肾病，其由远端肾单位中的经上皮氯化钠重吸收紊乱引起。已在NKCC 2（Na+-K+-2Cl-）协同转运蛋白和ROMK钾通道（在顶端氯化钠吸收过程中合作）以及ClC-Kb氯化物通道（介导基底侧氯化物释放）中发现了突变。最近，在BSND中描述了barttin（一种与任何已知离子转运蛋白或通道无关的蛋白质）的突变，BSND是与感音神经性耳聋相关的Bartter综合征的一种变体。在这里，我们表明，barttin作为ClC-K氯离子通道的激活剂。barttin与ClC-K一起在爪蟾卵母细胞中表达增加了ClC-K电流幅度，改变了ClC-K的生物物理性质，并增强了细胞膜中ClC-K的丰度。免疫共沉淀显示barttin与ClC-K的直接相互作用。我们对大鼠肾切片进行原位杂交，并对显微切割的肾单位片段进行RT-PCR分析，以证明barttin、ClC-K1和ClC-K2沿着远端肾单位共表达。BSND相关点突变的功能分析显示，受损的ClC-K激活barttin。结果表明，调节CLC氯离子通道的辅助蛋白，并表明，ClC-K激活barttin是必要的充分的肾小管盐重吸收。
Abstract. The term Bartter syndrome encompasses a heterogeneous group of autosomal recessive salt-losing nephropathies that are caused by disturbed transepithelial sodium chloride reabsorption in the distal nephron. Mutations have been identified in the NKCC2 (Na+-K+-2Cl–) cotransporter and ROMK potassium channel, which cooperate in the process of apical sodium chloride uptake, and ClC-Kb chloride channels, which mediate basolateral chloride release. Recently, mutations in barttin, a protein not related to any known ion transporter or channel, were described in BSND, a variant of Bartter syndrome associated with sensorineural deafness. Here we show that barttin functions as an activator of ClC-K chloride channels. Expression of barttin together with ClC-K in Xenopus oocytes increased ClC-K current amplitude, changed ClC-K biophysical properties, and enhanced ClC-K abundance in the cell membrane. Co-immunoprecipitation revealed a direct interaction of barttin with ClC-K. We performed in situ hybridization on rat kidney slices and RT-PCR analysis on microdissected nephron segments to prove co-expression of barttin, ClC-K1 and ClC-K2 along the distal nephron. Functional analysis of BSND-associated point mutations revealed impaired ClC-K activation by barttin. The results demonstrate regulation of a CLC chloride channel by an accessory protein and indicate that ClC-K activation by barttin is required for adequate tubular salt reabsorption.
DOI：
10.1152/ajprenal.1997.273.4.f650
发表时间：
1997-10-01
影响因子：
4.2
作者：
Schafer, JA;Watkins, ML;Schlatter, E
通讯作者：
Schlatter, E