title: Receptor-interacting protein 140 attenuates endoplasmic reticulum stress in neurons and protects against cell death.
abstract: Inositol 1, 4, 5-trisphosphate receptor (IP3R)-mediated Ca(2+) release from the endoplasmic reticulum (ER) triggers many physiological responses in neurons, and when uncontrolled can cause ER stress that contributes to neurological disease. Here we show that the unfolded protein response (UPR) in neurons induces rapid translocation of nuclear receptor-interacting protein 140 (RIP140) to the cytoplasm. In the cytoplasm, RIP140 localizes to the ER by binding to the IP3R. The carboxyl-terminal RD4 domain of RIP140 interacts with the carboxyl-terminal gate-keeping domain of the IP3R. This molecular interaction disrupts the IP3R's 'head-tail' interaction, thereby suppressing channel opening and attenuating IP3R-mediated Ca(2+) release. This contributes to a rapid suppression of the ER stress response and provides protection from apoptosis in both hippocampal neurons in vitro and in an animal model of ER stress. Thus, RIP140 translocation to the cytoplasm is an early response to ER stress and provides protection against neuronal death.
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors: Xudong
authors: X
authors: Feng
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors: Kelly A
authors: KA
authors: Krogh
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors: Cheng-Ying
authors: CY
authors: Wu
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors: Yi-Wei
authors: YW
authors: Lin
authors: 1] Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA [2] Department of Neurosurgery, Chang-Gung Memorial Hospital and University, Tao-Yuan 333, Taiwan, Republic of China.
authors: Hong-Chieh
authors: HC
authors: Tsai
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors: Stanley A
authors: SA
authors: Thayer
authors: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors: Li-Na
authors: LN
authors: Wei
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000502:physiology*; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism*
chemical_list: D056971:Nuclear Receptor Co-Repressor 1