Truncated KCNQ1 mutant, A178fs/105, forms hetero-multimer channel with wild-type causing a dominant-negative suppression due to trafficking defect
Truncated KCNQ1 mutant, A178fs/105, forms hetero-multimer channel with wild-type causing a dominant-negative suppression due to trafficking defect
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DOI：
10.1016/j.febslet.2004.08.018
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发表时间：
2004-09-10
期刊：
影响因子：
3.5
通讯作者：
Hiraoka, M
中科院分区：
文献类型：
--
作者：
Aizawa, Y;Ueda, K;Hiraoka, M
我们鉴定了一种新的突变Ala 178 fs/105，其缺失KCNQ 1通道的S3-S6和C-末端部分。在COS-7细胞中表达的Ala 178 fs/105-KCNQ 1无电流表达。与野生型（WT）的共表达揭示了显性负效应，这表明突变体和WT形成异源多聚体。激光共聚焦显微镜显示Ala 178 fs/105-KCNQ 1蛋白在细胞内滞留。与单独的WT相比，突变体和WT的共表达也增加了通道蛋白的细胞内保留。我们的研究结果表明，LQT 1的一个新的机制，截短的S1-S2 KCNQ 1突变体形成异源多聚体，并导致显性负效应，由于运输缺陷。(C)2004年由Elsevier B. V.代表欧洲生物化学学会联合会出版。
We identified a novel mutation Ala178fs/105 missing S3-S6 and C-terminus portions of KCNQl channel. Ala178fs/105-KCNQ1 expressed in COS-7 cells demonstrated no current expression. Co-expression with wild-type (WT) revealed a dominant-negative effect, which suggests the formation of hetero-multimer by mutant and WT. Confocal laser microscopy displayed intracellular retention of Ala178fs/105-KCNQ1 protein. Co-expression of the mutant and WT also increased intracellular retention of channel protein compared to WT alone. Our findings suggest a novel mechanism for LQT1 that the truncated S1-S2 KCNQ1 mutant forms hetero-multimer and cause a dominant-negative effect due to trafficking defect. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.