Truncated KCNQ1 mutant, A178fs/105, forms hetero‐multimer channel with wild‐type causing a dominant‐negative suppression due to trafficking defect
- 21 August 2004
- journal article
- case report
- Published by Wiley in FEBS Letters
- Vol. 574 (1-3), 145-150
- https://doi.org/10.1016/j.febslet.2004.08.018
Abstract
We identified a novel mutation Ala178fs/105 missing S3-S6 and C-terminus portions of KCNQ1 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.Keywords
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