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Truncated KCNQ1 mutant, A178fs/105, forms hetero‐multimer channel with wild‐type causing a dominant‐negative suppression due to trafficking defect
Author(s) -
Aizawa Yoshiyasu,
Ueda Kazuo,
Wu Long-mei,
Inagaki Natsuko,
Hayashi Takeharu,
Takahashi Megumi,
Ohta Masaaki,
Kawano Seiko,
Hirano Yuji,
Yasunami Michio,
Aizawa Yoshifusa,
Kimura Akinori,
Hiraoka Masayasu
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.08.018
Subject(s) - mutant , intracellular , mutation , microbiology and biotechnology , wild type , chemistry , biology , biophysics , genetics , gene
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.