β1- and β3- voltage-gated sodium channel subunits modulate cell surface expression and glycosylation of Nav1.7 in HEK293 cells

Laedermann, Cédric J; Syam, Ninda; Pertin, Marie; Decosterd, Isabelle; Abriel, Hugues (2013). β1- and β3- voltage-gated sodium channel subunits modulate cell surface expression and glycosylation of Nav1.7 in HEK293 cells. Frontiers in cellular neuroscience, 7, p. 137. Lausanne: Frontiers Research Foundation 10.3389/fncel.2013.00137

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Ionenkanalkrankheiten
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Ionenkanalkrankheiten

UniBE Contributor:

Laedermann, Cédric; Syam, Ninda Ratna Maharani and Abriel, Hugues

ISSN:

1662-5102

Publisher:

Frontiers Research Foundation

Funders:

[4] Swiss National Science Foundation

Projects:

[12] In vivo relevance of the PY and PDZ-domain binding motifs of the cardiac sodium channel Nav1.5 Official URL

Language:

English

Submitter:

Hugues Abriel

Date Deposited:

24 Oct 2013 22:51

Last Modified:

30 Sep 2019 14:42

Publisher DOI:

10.3389/fncel.2013.00137

PubMed ID:

24009557

Uncontrolled Keywords:

Navs β-subunits biophysical properties glycosylation trafficking voltage-gated sodium channels (Navs)

BORIS DOI:

10.7892/boris.38729

URI:

https://boris.unibe.ch/id/eprint/38729

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