Liddle's syndrome caused by a novel mutation in the proline-rich PY motif of the epithelial sodium channel β-subunit
Liddle's syndrome caused by a novel mutation in the proline-rich PY motif of the epithelial sodium channel β-subunit
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DOI：
10.1210/jc.2004-1027
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发表时间：
2005-01-01
影响因子：
5.8
通讯作者：
Shimamoto, K
中科院分区：
文献类型：
--
作者：
Furuhashi, M;Kitamura, K;Shimamoto, K
Liddle综合征是一种常染色体显性形式的盐敏感性高血压，已被证明是由阿米洛利敏感性上皮钠通道（ENaC）中的错义或移码突变引起的，ENaC由三个亚基组成：α，β和γ。所有疾病突变都去除或改变β-或γ-ENaC的目标富含脯氨酸的PPPxY序列（PY基序）的氨基酸，并导致通道活性增加。在这份报告中，我们提出了一个家庭与利德尔综合征的异常是由一个新的错义突变，P616 R，在PY基序的β ENaC。使用在非洲爪蟾卵母细胞中表达的P616 R突变体的功能研究显示，与野生型相比，阿米洛利敏感性钠通道活性增加约6倍。这些发现提供了额外的临床证据，保守的PY基序是至关重要的ENaC活性的调节。
Liddle's syndrome is an autosomal dominant form of salt-sensitive hypertension and has been shown to be caused by missense or frameshift mutations in the amiloride-sensitive epithelial sodium channel (ENaC), which is composed of three subunits: alpha, beta, and gamma. All disease mutations either remove or alter amino acids of the target proline-rich PPPxY sequence (PY motif) of beta- or gamma-ENaC and result in increased channel activity. In this report, we present a family with Liddle's syndrome whose abnormality is caused by a novel missense mutation, P616R, in the PY motif of the betaENaC. Functional studies using the P616R mutant expressed in Xenopus oocytes showed an approximately 6-fold increase in the amiloride-sensitive sodium channel activity compared with that of the wild type. These findings provide additional clinical evidence that a conserved PY motif is critically important for the regulation of ENaC activity.