The novel C-terminal KCNQ1 mutation M520R alters protein trafficking.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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
Originalsprog | Engelsk |
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Tidsskrift | Biochemical and Biophysical Research Communications |
Vol/bind | 358 |
Udgave nummer | 1 |
Sider (fra-til) | 304-10 |
Antal sider | 6 |
ISSN | 0006-291X |
DOI | |
Status | Udgivet - 2007 |
ID: 2983028