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ID 116629
Nguyen, Dinh Thi Kanazawa University
Le, Thuong Manh Kanazawa University|Hanoi Medical University
Hattori, Tsuyoshi Kanazawa University
Takarada‑Iemata, Mika Kanazawa University
Ishii, Hiroshi Kanazawa University
Roboon, Jureepon Kanazawa University
Tamatani, Takashi Kanazawa University
Kannon, Takayuki Kanazawa University
Hosomichi, Kazuyoshi Kanazawa University
Taniuchi, Shusuke Tokushima University
Tanaka, Takashi Kanazawa Medical University
Kato, Nobuo Kanazawa Medical University
Saito, Shunsuke Kyoto University
Mori, Kazutoshi Kyoto University
Hori, Osamu Kanazawa University
Content Type
Journal Article
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.
Journal Title
Scientific Reports
Springer Nature
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Medical Sciences
Institute of Advanced Medical Sciences