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  2. 水生生物研究所
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  5. 期刊论文
Deficiency in the membrane protein Tmbim3a/Grinaa initiates cold-induced ER stress and cell death by activating an intrinsic apoptotic pathway in zebrafish

文献类型：期刊论文

作者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
出版日期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
DOI10.1074/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.
WOS关键词ENDOPLASMIC-RETICULUM ; BAX INHIBITOR-1 ; SERCA PUMP ; CALCIUM ; IDENTIFICATION ; MODULATION ; RELEASE ; GENE ; CA2+
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研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000478717600009
出版者AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
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
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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来源：水生生物研究所

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