The Cacna1h mutation in the GAERS model of absence epilepsy enhances T-type Ca2+ currents by altering calnexin-dependent trafficking of Ca(v)3.2 channels

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00479170" target="_blank" >RIV/61388963:_____/17:00479170 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41598-017-11591-5" target="_blank" >https://www.nature.com/articles/s41598-017-11591-5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-017-11591-5" target="_blank" >10.1038/s41598-017-11591-5</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The Cacna1h mutation in the GAERS model of absence epilepsy enhances T-type Ca2+ currents by altering calnexin-dependent trafficking of Ca(v)3.2 channels

Popis výsledku v původním jazyce

Low-voltage-activated T-type calcium channels are essential contributors to the functioning of thalamocortical neurons by supporting burst-firing mode of action potentials. Enhanced T-type calcium conductance has been reported in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) and proposed to be causally related to the overall development of absence seizure activity. Here, we show that calnexin, an endoplasmic reticulum integral membrane protein, interacts with the III-IV linker region of the Ca(v)3.2 channel to modulate the sorting of the channel to the cell surface. We demonstrate that the GAERS missense mutation located in the Ca(v)3.2 III-IV linker alters the Ca(v)3.2/calnexin interaction, resulting in an increased surface expression of the channel and a concomitant elevation in calcium influx. Our study reveals a novel mechanism that controls the expression of T-type channels, and provides a molecular explanation for the enhancement of T-type calcium conductance in GAERS.

Název v anglickém jazyce

The Cacna1h mutation in the GAERS model of absence epilepsy enhances T-type Ca2+ currents by altering calnexin-dependent trafficking of Ca(v)3.2 channels

Popis výsledku anglicky

Low-voltage-activated T-type calcium channels are essential contributors to the functioning of thalamocortical neurons by supporting burst-firing mode of action potentials. Enhanced T-type calcium conductance has been reported in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) and proposed to be causally related to the overall development of absence seizure activity. Here, we show that calnexin, an endoplasmic reticulum integral membrane protein, interacts with the III-IV linker region of the Ca(v)3.2 channel to modulate the sorting of the channel to the cell surface. We demonstrate that the GAERS missense mutation located in the Ca(v)3.2 III-IV linker alters the Ca(v)3.2/calnexin interaction, resulting in an increased surface expression of the channel and a concomitant elevation in calcium influx. Our study reveals a novel mechanism that controls the expression of T-type channels, and provides a molecular explanation for the enhancement of T-type calcium conductance in GAERS.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

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

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Scientific Reports

ISSN

2045-2322

e-ISSN

—

Svazek periodika

7

Číslo periodika v rámci svazku

Sep 14

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

—

Kód UT WoS článku

000410739000011

EID výsledku v databázi Scopus

2-s2.0-85029477490