Functional studies of human skin disease- and deafness-associated connexin 30 mutations
Functional studies of human skin disease- and deafness-associated connexin 30 mutations
复制标题
DOI：
10.1016/s0006-291x(02)02517-2
复制
发表时间：
2002-11-15
影响因子：
3.1
通讯作者：
Kelsell, DP
中科院分区：
文献类型：
--
作者：
Common, JEA;Becker, D;Kelsell, DP
Connexin 30 （COO）是间隙连接复合物的一个组成部分。编码Cx30的GJB6基因的显性和隐性突变与多种主要影响表皮、头发、指甲和/或内耳的人类遗传性疾病有关。与不同GJB6突变相关的疾病的潜在机制，如间隙连接介导的细胞间通讯的破坏，尚不清楚。为了了解这些疾病的机制，在角质形成细胞系和HeLa细胞中进行了转染研究，使用EGFP标记的野生型Cx30和突变型Cx30构建物，其中包含显性疾病相关的GJB6突变。对于所研究的所有三种与皮肤病相关的Cx30突变，观察到蛋白质向质膜的运输受损，从而阻止了功能性Cx30间隙连接的形成。相比之下，耳聋相关突变T5M-Cx30/EGFP转运到膜上，但在染料转移研究中观察到缺陷通道活性。(C) 2002 Elsevier Science （USA）。版权所有。
Connexin 30 (COO) is a component of the gap junction complex. Dominant and recessive mutations in the GJB6 gene encoding Cx30 are associated with a variety of human inherited diseases primarily affecting the epidermis, hair, nail, and/or the inner ear. The underlying mechanism of disease associated with different GJB6 mutations such as the disruption of gap junction mediated intercellular communication is unknown. Towards understanding these disease mechanisms, transfection studies were performed in a keratinocyte cell line and in HeLa cells using EGFP tagged wildtype Cx30 and mutant Cx30 constructs harbouring dominant disease-associated GJB6 mutations. For all three of the skin disease-associated Cx30 mutations investigated, impaired trafficking of the protein to the plasma membrane was observed thus preventing the formation of functional Cx30 gap junctions. In contrast, the deafness-associated mutation T5M-Cx30/EGFP trafficked to the membrane but defective channel activity was observed following dye transfer studies. (C) 2002 Elsevier Science (USA). All rights reserved.