Cooperative roles of glucose and asparagine-linked glycosylation in T-type calcium channel expression

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00469487" target="_blank" >RIV/61388963:_____/16:00469487 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s00424-016-1881-y" target="_blank" >http://dx.doi.org/10.1007/s00424-016-1881-y</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00424-016-1881-y" target="_blank" >10.1007/s00424-016-1881-y</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cooperative roles of glucose and asparagine-linked glycosylation in T-type calcium channel expression

Popis výsledku v původním jazyce

T-type calcium channels are key contributors to neuronal physiology where they shape electrical activity of nerve cells and contribute to the release of neurotransmitters. Enhanced T-type channel expression has been causally linked to a number of pathological conditions including peripheral painful diabetic neuropathy. Recently, it was demonstrated that asparagine-linked glycosylation not only plays an essential role in regulating cell surface expression of Ca(v)3.2 channels, but may also support glucose-dependent potentiation of T-type currents. However, the underlying mechanisms by which N-glycosylation and glucose levels modulate the expression of T-type channels remain elusive. In the present study, we show that site-specific N-glycosylation of Ca(v)3.2 is essential to stabilize expression of the channel at the plasma membrane. In contrast, elevated external glucose concentration appears to potentiate intracellular forward trafficking of the channel to the cell surface, resulting in an increased steady-state expression of the channel protein at the plasma membrane. Collectively, our study indicates that glucose and N-glycosylation act in concert to control the expression of Ca(v)3.2 channels, and that alteration of these mechanisms may contribute to the altered expression of T-type channels in pathological conditions.

Název v anglickém jazyce

Cooperative roles of glucose and asparagine-linked glycosylation in T-type calcium channel expression

Popis výsledku anglicky

T-type calcium channels are key contributors to neuronal physiology where they shape electrical activity of nerve cells and contribute to the release of neurotransmitters. Enhanced T-type channel expression has been causally linked to a number of pathological conditions including peripheral painful diabetic neuropathy. Recently, it was demonstrated that asparagine-linked glycosylation not only plays an essential role in regulating cell surface expression of Ca(v)3.2 channels, but may also support glucose-dependent potentiation of T-type currents. However, the underlying mechanisms by which N-glycosylation and glucose levels modulate the expression of T-type channels remain elusive. In the present study, we show that site-specific N-glycosylation of Ca(v)3.2 is essential to stabilize expression of the channel at the plasma membrane. In contrast, elevated external glucose concentration appears to potentiate intracellular forward trafficking of the channel to the cell surface, resulting in an increased steady-state expression of the channel protein at the plasma membrane. Collectively, our study indicates that glucose and N-glycosylation act in concert to control the expression of Ca(v)3.2 channels, and that alteration of these mechanisms may contribute to the altered expression of T-type channels in pathological conditions.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Pflugers Archiv - European Journal of Physiology

ISSN

0031-6768

e-ISSN

—

Svazek periodika

468

Číslo periodika v rámci svazku

11/12

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

15

Strana od-do

1837-1851

Kód UT WoS článku

000389834100005

EID výsledku v databázi Scopus

2-s2.0-84988723398