The novel C-terminal KCNQ1 mutation M520R alters protein trafficking.

Research output: Contribution to journalJournal articleResearchpeer-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
Original languageEnglish
JournalBiochemical and Biophysical Research Communications
Issue number1
Pages (from-to)304-10
Number of pages6
Publication statusPublished - 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