Details

Autor(en) / Beteiligte

• Proft, Juliane
• Rzhepetskyy, Yuriy
• Lazniewska, Joanna
• Zhang, Fang-Xiong
• Cain, Stuart M.
• Snutch, Terrance P.
• Zamponi, Gerald W.
• Weiss, Norbert

Titel

The Cacna1h mutation in the GAERS model of absence epilepsy enhances T-type Ca2+ currents by altering calnexin-dependent trafficking of Cav3.2 channels

Ist Teil von

• Scientific reports, 2017-09, Vol.7 (1), p.1-13, Article 11513

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2017

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.