| 著者 |
Nguyen, Dinh Thi
Le, Thuong Manh
ハットリ, ツヨシ
タカラダ イエマタ, ミカ
イシイ, ヒロシ
Roboon, Jureepon
タマタニ, タカシ
カンノン, タカユキ
ホソミチ, カズヨシ
田嶋, 敦
WEKO
481
e-Rad_Researcher
10396864
| ja |
田嶋, 敦
田嶋, 敦
ISNI
|
| ja-Kana |
タジマ, アツシ
タジマ, アツシ
|
| en |
Tajima, Atsushi
Tajima, Atsushi
|
Search repository
タニウチ, シュウスケ
三宅, 雅人
親泊, 政一
タナカ, タカシ
カトウ, ノブオ
サイトウ, シュンスケ
モリ, カズトシ
ホリ, オサム
|
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内容記述 |
While ATF6α plays a central role in the endoplasmic reticulum (ER) stress response, the function of its paralogue ATF6β remains elusive, especially in the central nervous system (CNS). Here, we demonstrate that ATF6β is highly expressed in the hippocampus of the brain, and specifically regulates the expression of calreticulin (CRT), a molecular chaperone in the ER with a high Ca2+-binding capacity. CRT expression was reduced to ~ 50% in the CNS of Atf6b−/− mice under both normal and ER stress conditions. Analysis using cultured hippocampal neurons revealed that ATF6β deficiency reduced Ca2+ stores in the ER and enhanced ER stress-induced death. The higher levels of death in Atf6b−/− neurons were recovered by ATF6β and CRT overexpressions, or by treatment with Ca2+-modulating reagents such as BAPTA-AM and 2-APB, and with an ER stress inhibitor salubrinal. In vivo, kainate-induced neuronal death was enhanced in the hippocampi of Atf6b−/− and Calr+/− mice, and restored by administration of 2-APB and salubrinal. These results suggest that the ATF6β-CRT axis promotes neuronal survival under ER stress and excitotoxity by improving intracellular Ca2+ homeostasis. |
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権利情報 |
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
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