β1- and β3- voltage-gated sodium channel subunits modulate cell surface expression and glycosylation of Nav1.7 in HEK293 cells.
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Download: BIB_FFFC75AB3303.P001.pdf (3306.82 [Ko])
State: Public
Version: author
State: Public
Version: author
Serval ID
serval:BIB_FFFC75AB3303
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
β1- and β3- voltage-gated sodium channel subunits modulate cell surface expression and glycosylation of Nav1.7 in HEK293 cells.
Journal
Frontiers in Cellular Neuroscience
ISSN
1662-5102 (Electronic)
ISSN-L
1662-5102
Publication state
Published
Issued date
2013
Volume
7
Number
137
Pages
1-12
Language
english
Notes
Publication types: Journal ArticlePublication Status: epublish. PDF type: Original research article
Abstract
Voltage-gated sodium channels (Navs) are glycoproteins composed of a pore-forming α-subunit and associated β-subunits that regulate Nav α-subunit plasma membrane density and biophysical properties. Glycosylation of the Nav α-subunit also directly affects Navs gating. β-subunits and glycosylation thus comodulate Nav α-subunit gating. We hypothesized that β-subunits could directly influence α-subunit glycosylation. Whole-cell patch clamp of HEK293 cells revealed that both β1- and β3-subunits coexpression shifted V ½ of steady-state activation and inactivation and increased Nav1.7-mediated I Na density. Biotinylation of cell surface proteins, combined with the use of deglycosydases, confirmed that Nav1.7 α-subunits exist in multiple glycosylated states. The α-subunit intracellular fraction was found in a core-glycosylated state, migrating at ~250 kDa. At the plasma membrane, in addition to the core-glycosylated form, a fully glycosylated form of Nav1.7 (~280 kDa) was observed. This higher band shifted to an intermediate band (~260 kDa) when β1-subunits were coexpressed, suggesting that the β1-subunit promotes an alternative glycosylated form of Nav1.7. Furthermore, the β1-subunit increased the expression of this alternative glycosylated form and the β3-subunit increased the expression of the core-glycosylated form of Nav1.7. This study describes a novel role for β1- and β3-subunits in the modulation of Nav1.7 α-subunit glycosylation and cell surface expression.
Pubmed
Web of science
Open Access
Yes
Create date
10/10/2013 18:00
Last modification date
20/08/2019 17:30