The novel C-terminal KCNQ1 mutation M520R alters protein trafficking.
Research output: Contribution to journal › Journal article › Research › peer-review
The long QT-syndrome is characterized by a prolongation of the QT-interval and tachyarrhythmias causing syncopes and sudden death. We identified the missense mutation M520R in the calmodulin binding domain of the Kv7.1 channel from a German family with long QT-syndrome. Heterologous expression of the mutant did not reveal any whole-cell currents independent of the auxiliary subunit KCNE1. Co-expression of the wild-type Kv7.1 channels and the mutant showed that the mutant did not have a dominant negative effect. In immunocytochemical assays of transfected COS-1 cells wild-type Kv7.1 showed an immunopositive labeling of the plasma membrane. For M520R no plasma membrane staining was visible, instead a strong signal in the ER was observed. These results indicate that the LQT1 mutation M520R leads to ER-retention and dysfunctional trafficking of the mutant channel resulting in haploinsufficiency.
Udgivelsesdato: 2007-Jun-22
Udgivelsesdato: 2007-Jun-22
Original language | English |
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Journal | Biochemical and Biophysical Research Communications |
Volume | 358 |
Issue number | 1 |
Pages (from-to) | 304-10 |
Number of pages | 6 |
ISSN | 0006-291X |
DOIs | |
Publication status | Published - 2007 |
Bibliographical note
Keywords: Adult; Amino Acid Sequence; Animals; CHO Cells; COS Cells; Cell Membrane; Cercopithecus aethiops; Cricetinae; Cricetulus; Endoplasmic Reticulum; Female; Humans; KCNQ1 Potassium Channel; Long QT Syndrome; Middle Aged; Molecular Sequence Data; Mutation, Missense; Patch-Clamp Techniques; Pedigree; Protein Structure, Tertiary; Protein Transport
ID: 2983028