N-glycosylation-dependent regulation of hK17.1 currents.

08:00 EDT 10th April 2019 | BioPortfolio

Summary of "N-glycosylation-dependent regulation of hK17.1 currents."

Two-pore-domain potassium (K) channels mediate potassium background currents that stabilize the resting membrane potential and facilitate action potential repolarization. In the human heart, hK17.1 channels are predominantly expressed in the atria and Purkinje cell. Reduced atrial hK17.1 protein levels were described in patients with atrial fibrillation or heart failure. Genetic alterations in hK17.1 were associated with cardiac conduction disorders. Little is known about posttranslational modifications of hK17.1. Here, we characterized glycosylation of hK17.1 and investigated how glycosylation alters its surface expression and activity. Wild-type (WT) hK17.1 channels and channels lacking specific glycosylation sites, were expressed in Xenopus laevis oocytes, HEK-293T cells and HeLa cells. N-glycosylation was disrupted using N-glycosidase F and tunicamycin. hK17.1 expression and activity were assessed using immunoblot analysis and two-electrode voltage-clamp technique. hK17.1 channel subunits harbor two functional N-glycosylation sites at position N65 and N94. In hemi-glycosylated hK17.1 channels, functionality and membrane trafficking remain preserved. Disruption of both N-glycosylation sites results in loss of hK17.1 currents, presumably caused by impaired surface expression. This study confirms di-glycosylation of hK17.1 channel subunits and its pivotal role in cell surface targeting. Our findings underline the functional relevance of N-glycosylation in biogenesis and membrane trafficking of ion channels.


Journal Details

This article was published in the following journal.

Name: Molecular biology of the cell
ISSN: 1939-4586
Pages: mbcE18100687


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