NDLI: Evolutionary emergence of N-glycosylation as a variable promoter of HCN channel surface expression.

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Evolutionary emergence of N-glycosylation as a variable promoter of HCN channel surface expression.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hegle, Andrew P. Nazzari, Hamed Roth, Andrew Angoli, Damiano Accili, Eric A.
Description	Country affiliation: Canada Author Affiliation: Hegle AP ( Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada.)
Abstract	All four mammalian hyperpolarization-activated cyclic nucleotide-modulated (HCN) channel isoforms have been shown to undergo N-linked glycosylation in the brain. With the mouse HCN2 isoform as a prototype, HCN channels have further been suggested to require N-glycosylation for function, a provocative finding that would make them unique in the voltage-gated potassium channel superfamily. Here, we show that both the HCN1 and HCN2 isoforms are also predominantly N-glycosylated in the embryonic heart, where they are found in significant amounts and where HCN-mediated currents are known to regulate beating frequency. Surprisingly, we find that N-glycosylation is not required for HCN2 function, although its cell surface expression is highly dependent on the presence of N-glycans. Comparatively, disruption of N-glycosylation only modestly impacts cell surface expression of HCN1 and leaves permeation and gating functions almost unchanged. This difference between HCN1 and HCN2 is consistent with evolutionary trajectories that diverged in an isoform-specific manner after gene duplication from a common HCN ancestor that lacked N-glycosylation and was able to localize efficiently to the cell surface.
File Format	HTM / HTML
ISSN	03636143
e-ISSN	15221563
Journal	American Journal of Physiology - Cell Physiology
Issue Number	5
Volume Number	298
Language	English
Publisher	American Physiological Society
Publisher Date	2010-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cell Biology Cell Membrane Metabolism Cyclic Nucleotide-gated Cation Channels Genetics Ion Channels Potassium Channels Amino Acid Sequence Amino Acid Substitution Animals Cho Cells Cricetinae Cricetulus Embryo, Mammalian Evolution, Molecular Gene Expression Regulation Glycosylation Heart Embryology Hyperpolarization-activated Cyclic Nucleotide-gated Channels Mice Molecular Sequence Data Myocardium Phylogeny Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Physiology

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