Nedd4-2-dependent ubiquitylation and regulation of the cardiac potassium channel hERG1.

Details

Serval ID
serval:BIB_01A640BC771F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Nedd4-2-dependent ubiquitylation and regulation of the cardiac potassium channel hERG1.
Journal
Journal of Molecular and Cellular Cardiology
Author(s)
Albesa M., Grilo L.S., Gavillet B., Abriel H.
ISSN
1095-8584 (Electronic)
ISSN-L
0022-2828
Publication state
Published
Issued date
2011
Volume
51
Number
1
Pages
90-98
Language
english
Abstract
The voltage-gated cardiac potassium channel hERG1 (human ether-à-gogo-related gene 1) plays a key role in the repolarization phase of the cardiac action potential (AP). Mutations in its gene, KCNH2, can lead to defects in the biosynthesis and maturation of the channel, resulting in congenital long QT syndrome (LQTS). To identify the molecular mechanisms regulating the density of hERG1 channels at the plasma membrane, we investigated channel ubiquitylation by ubiquitin ligase Nedd4-2, a post-translational regulatory mechanism previously linked to other ion channels. We found that whole-cell hERG1 currents recorded in HEK293 cells were decreased upon neural precursor cell expressed developmentally down-regulated 4-2 (Nedd4-2) co-expression. The amount of hERG1 channels in total HEK293 lysates and at the cell surface, as assessed by Western blot and biotinylation assays, respectively, were concomitantly decreased. Nedd4-2 and hERG1 interact via a PY motif located in the C-terminus of hERG1. Finally, we determined that Nedd4-2 mediates ubiquitylation of hERG1 and that deletion of this motif affects Nedd4-2-dependent regulation. These results suggest that ubiquitylation of the hERG1 protein by Nedd4-2, and its subsequent down-regulation, could represent an important mechanism for modulation of the duration of the human cardiac action potential.
Pubmed
Web of science
Create date
29/06/2011 12:35
Last modification date
20/08/2019 12:23
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