A role for CBS domain 2 in trafficking of chloride channel CLC-5
A role for CBS domain 2 in trafficking of chloride channel CLC-5
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DOI：
10.1016/j.bbrc.2003.09.057
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发表时间：
2003-10-17
影响因子：
3.1
通讯作者：
Sayer, J
中科院分区：
文献类型：
--
作者：
Carr, G;Simmons, N;Sayer, J
CLC-5是CLC家族电压门控氯离子通道的一员。破坏CLC-5的突变可导致邓特病，这是一种x连锁肾小管疾病，以低分子量蛋白尿、高钙尿、肾钙质沉着症和肾结石为特征。对CLC-5的序列分析显示，该蛋白具有746个氨基酸，具有胞内氨基端、跨膜跨结构域和胞内羧基端两个CBS结构域。CBS结构域涉及细胞内靶向和运输以及蛋白质-蛋白质相互作用。我们研究了三种自然发生的CLC-5突变体的亚细胞定位，它们都导致一个截断的蛋白质，破坏第二个CBS结构域。这些突变体不能正常运输到酸性核内体，但保留在核周室中，与高尔基复合体共定位。这是首次发现CLC-5 CBS结构域突变的细胞发病机制。(C) 2003 Elsevier Inc.版权所有。
CLC-5 is a member of the CLC family of voltage-gated chloride channels. Mutations disrupting CLC-5 lead to Dent's disease, an X-linked renal tubular disorder, characterised by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, and renal stones. Sequence analysis of CLC-5 reveals a 746 amino acid protein with an intracellular amino-terminus, transmembrane spanning domains, and two CBS domains within its intracellular carboxy-terminus. CBS domains have been implicated in intracellular targetting and trafficking as well as protein-protein interactions. We investigate subcellular localisation of three naturally occurring CLC-5 mutants which all lead to a truncated protein, disrupting the second CBS domain. These mutants are unable to traffic normally to acidic endosomes but are retained in perinuclear compartments, colocalising with the Golgi complex. This is the first identification of the cellular pathogenesis of CBS domain mutations of CLC-5. (C) 2003 Elsevier Inc. All rights reserved.