Modulation of Ca(v)3.2 T-type calcium channel permeability by asparagine-linked glycosylation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F16%3A00461232" target="_blank" >RIV/61388963:_____/16:00461232 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1080/19336950.2016.1138189" target="_blank" >http://dx.doi.org/10.1080/19336950.2016.1138189</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/19336950.2016.1138189" target="_blank" >10.1080/19336950.2016.1138189</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Modulation of Ca(v)3.2 T-type calcium channel permeability by asparagine-linked glycosylation

Popis výsledku v původním jazyce

Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. Currently, little is known about the cellular mechanisms controlling the expression and function of T-type channels. Asparagine-linked glycosylation has recently emerged as an essential signaling pathway by which the cellular environment can control expression of T-type channels. However, the role of N-glycans in the conducting function of T-type channels remains elusive. In the present study, we used human Ca(v)3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. Patch-clamp recordings of gating currents revealed that N-glycans attached to hCa(v)3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. Our data suggest that modulation of N-linked glycosylation of hCa(v)3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states.

Název v anglickém jazyce

Modulation of Ca(v)3.2 T-type calcium channel permeability by asparagine-linked glycosylation

Popis výsledku anglicky

Low-voltage-gated T-type calcium channels are expressed throughout the nervous system where they play an essential role in shaping neuronal excitability. Defects in T-type channel expression have been linked to various neuronal disorders including neuropathic pain and epilepsy. Currently, little is known about the cellular mechanisms controlling the expression and function of T-type channels. Asparagine-linked glycosylation has recently emerged as an essential signaling pathway by which the cellular environment can control expression of T-type channels. However, the role of N-glycans in the conducting function of T-type channels remains elusive. In the present study, we used human Ca(v)3.2 glycosylation-deficient channels to assess the role of N-glycosylation on the gating of the channel. Patch-clamp recordings of gating currents revealed that N-glycans attached to hCa(v)3.2 channels have a minimal effect on the functioning of the channel voltage-sensor. In contrast, N-glycosylation on specific asparagine residues may have an essential role in the conducting function of the channel by enhancing the channel permeability and / or the pore opening of the channel. Our data suggest that modulation of N-linked glycosylation of hCa(v)3.2 channels may play an important physiological role, and could also support the alteration of T-type currents observed in disease states.

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

Channels

ISSN

1933-6950

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

175-184

Kód UT WoS článku

000374581700004

EID výsledku v databázi Scopus

2-s2.0-84978393937