Deficiency in the membrane protein Tmbim3a/Grinaa initiates cold-induced ER stress and cell death by activating an intrinsic apoptotic pathway in zebrafish | |
Chen, Kai1,2; Li, Xixi1,2; Song, Guili1; Zhou, Tong1,2; Long, Yong1; Li, Qing1; Zhong, Shan3; Cui, Zongbin1,4 | |
刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY |
2019-07-26 | |
卷号 | 294期号:30页码:11445-11457 |
关键词 | endoplasmic reticulum stress (ER stress) calcium intracellular release apoptosis zebrafish stress response apoptosis calcium homeostasis cold exposure endoplasmic reticulum stress calcium homeostasis Grinaa transmembrane BAX inhibitor motif (TMBIM) unfolded protein response (UPR) cell death |
DOI | 10.1074/jbc.RA119.007813 |
通讯作者 | Cui, Zongbin(zbcui@ihb.ac.cn) |
英文摘要 | Most members of the family of proteins containing a transmembrane BAX inhibitor motif (TMBIM) have anti-apoptotic activity, but their in vivo functions and intracellular mechanisms remain obscure. Here, we report that zebrafish Tmbim3a/Grinaa functions in the prevention of cold-induced endoplasmic reticulum (ER) stress and apoptosis. Using a gene-trapping approach, we obtained a mutant zebrafish line in which the expression of the tmbim3a/grinaa gene is disrupted by a Tol2 transposon insertion. Homozygous tmbim3a/grinaa mutant larvae exhibited time-dependently increased mortality and apoptosis under cold exposure (at 16 degrees C). Mechanistically, using immunofluorescence, fluorescence-based assessments of intracellular/mitochondrial Ca2+ levels, mitochondrial membrane potential measurements, and Ca2+-ATPase assays, we found that cold exposure suppresses sarcoplasmic/ER Ca2+-ATPase (SERCA) activity and induces the unfolded protein response (UPR) and ER stress. We also found that the cold-induced ER stress is increased in homozygous tmbim3a/grinaa mutant embryos. The cold-stress hypersensitivity of the tmbim3a/grinaa mutants was tightly associated with disrupted intracellular Ca2+ homeostasis, followed by mitochondrial Ca2+ overload and cytochrome c release, leading to the activation of caspase 9- and caspase-3-mediated intrinsic apoptotic pathways. Treatment of zebrafish larvae with the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N ',N '-tetraacetate-acetoxymethyl ester (BAPTA-AM) or with 2-aminoethoxydiphenyl borate (2-APB), an inhibitor of the calcium-releasing protein inositol 1,4,5-trisphosphate receptor (IP3R), alleviated cold-induced cell death. Together, these findings unveil a key role of Tmbim3a/Grinaa in relieving cold-induced ER stress and in protecting cells against caspase 9- and caspase 3-mediated apoptosis during zebrafish development. |
资助项目 | Science Fund for the Creative Research Group of the National Natural Science Foundation of China[31721005] ; National Natural Science Foundation of China[31872554] ; National Natural Science Foundation of China[31572610] ; National Natural Science Foundation of China[31772836] |
WOS关键词 | ENDOPLASMIC-RETICULUM ; BAX INHIBITOR-1 ; SERCA PUMP ; CALCIUM ; IDENTIFICATION ; MODULATION ; RELEASE ; GENE ; CA2+ |
WOS研究方向 | Biochemistry & Molecular Biology |
语种 | 英语 |
出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
WOS记录号 | WOS:000478717600009 |
资助机构 | Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; Science Fund for the Creative Research Group of the National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China |
内容类型 | 期刊论文 |
源URL | [http://ir.ihb.ac.cn/handle/342005/32050] |
专题 | 水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文 |
通讯作者 | Cui, Zongbin |
作者单位 | 1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Hubei, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Wuhan Univ, Dept Genet, Wuhan 430071, Hubei, Peoples R China 4.Chinese Acad Sci, Innovat Acad Seed Design, Beijing 100101, Peoples R China |
推荐引用方式 GB/T 7714 | Chen, Kai,Li, Xixi,Song, Guili,et al. Deficiency in the membrane protein Tmbim3a/Grinaa initiates cold-induced ER stress and cell death by activating an intrinsic apoptotic pathway in zebrafish[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2019,294(30):11445-11457. |
APA | Chen, Kai.,Li, Xixi.,Song, Guili.,Zhou, Tong.,Long, Yong.,...&Cui, Zongbin.(2019).Deficiency in the membrane protein Tmbim3a/Grinaa initiates cold-induced ER stress and cell death by activating an intrinsic apoptotic pathway in zebrafish.JOURNAL OF BIOLOGICAL CHEMISTRY,294(30),11445-11457. |
MLA | Chen, Kai,et al."Deficiency in the membrane protein Tmbim3a/Grinaa initiates cold-induced ER stress and cell death by activating an intrinsic apoptotic pathway in zebrafish".JOURNAL OF BIOLOGICAL CHEMISTRY 294.30(2019):11445-11457. |
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