| 题名 | 5-IP7 is a GPCR messenger mediating neural control of synaptotagmin-dependent insulin exocytosis and glucose homeostasis |
| 作者 | Zhang，Xiaozhe1  ; Li，Na1; Zhang，Jun1; Zhang，Yanshen2,3; Yang，Xiaoli1; Luo，Yifan1; Zhang，Bobo1; Xu，Zhixue1; Zhu，Zhenhua1; Yang，Xiuyan1; Yan，Yuan1; Lin，Biao1; Wang，Shen4; Chen，Da2,3; Ye，Caichao5; Ding，Yan6; Lou，Mingliang6; Wu，Qingcui6; Hou，Zhanfeng6; Zhang，Keren7; Liang，Ziming8; Wei，Anqi9; Wang，Bianbian9; Wang，Changhe9; Jiang，Nan8; Zhang，Wenqing5; Xiao，Guozhi10; Ma，Cong4; Ren，Yan7; Qi，Xiangbing6; Han，Weiping11,12; Wang，Chao2,3 ; Rao，Feng1
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| 通讯作者 | Wang，Chao; Rao，Feng |
| 共同第一作者 | Zhang，Xiaozhe; Li，Na; Zhang，Jun; Zhang，Yanshen; Yang，Xiaoli |
| 发表日期 | 2021
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| DOI | |
| 发表期刊 | |
| EISSN | 2522-5812
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| 卷号 | 3页码:1400-1414 |
| 摘要 | 5-diphosphoinositol pentakisphosphate (5-IP) is a signalling metabolite linked to various cellular processes. How extracellular stimuli elicit 5-IP signalling remains unclear. Here we show that 5-IP in β cells mediates parasympathetic stimulation of synaptotagmin-7 (Syt7)-dependent insulin release. Mechanistically, vagal stimulation and activation of muscarinic acetylcholine receptors triggers G–PLC–PKC−PKD-dependent signalling and activates IP6K1, the 5-IP synthase. Whereas both 5-IP and its precursor IP compete with PIP for binding to Syt7, Ca selectively binds 5-IP with high affinity, freeing Syt7 to enable fusion of insulin-containing vesicles with the cell membrane. β-cell-specific IP6K1 deletion diminishes insulin secretion and glucose clearance elicited by muscarinic stimulation, whereas mice carrying a phosphorylation-mimicking, hyperactive IP6K1 mutant display augmented insulin release, congenital hyperinsulinaemia and obesity. These phenotypes are absent in mice lacking Syt7. Our study proposes a new conceptual framework for inositol pyrophosphate physiology in which 5-IP acts as a GPCR second messenger at the interface between peripheral nervous system and metabolic organs, transmitting G-coupled GPCR stimulation to unclamp Syt7-dependent, and perhaps other, exocytotic events. |
| 相关链接 | [Scopus记录] |
| 收录类别 | |
| 语种 | 英语
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| 学校署名 | 第一
; 共同第一
; 通讯
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| WOS记录号 | WOS:000708364000004
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| Scopus记录号 | 2-s2.0-85117255934
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| 来源库 | Scopus
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| 引用统计 |
被引频次[WOS]：13
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| 成果类型 | 期刊论文 |
| 条目标识符 | http://sustech.caswiz.com/handle/2SGJ60CL/254270 |
| 专题 | 生命科学学院 理学院_物理系 量子科学与工程研究院 南方科技大学医学院 生命科学学院_生物系 南方科技大学第二附属医院 南方科技大学医学院_生物化学系 |
| 作者单位 | 1.School of Life Sciences,Southern University of Science and Technology,Shenzhen,China 2.Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics,Hefei National Laboratory for Physical Sciences at the Microscale,School of Life Sciences,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,China 3.Department of Neurology,the First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,China 4.Key Laboratory of Molecular Biophysics of the Ministry of Education,College of Life Science and Technology,Huazhong University of Science and Technology,Wuhan,China 5.Department of Physics and Shenzhen Institute for Quantum Science & Technology,Southern University of Science and Technology,Shenzhen,China 6.National Institute of Biological Sciences,Beijing,China 7.BGI-Shenzhen,Beishan Industrial Zone 11th building,Shenzhen,China 8.Department of Hepatic Surgery,the Third People′s Hospital of Shenzhen and the Second Affiliated Hospital of Southern University of Science and Technology,Shenzhen,China 9.Neuroscience Research Center,Institute of Mitochondrial Biology and Medicine,Key Laboratory of Biomedical Information Engineering of Ministry of Education,School of Life Science and Technology,Xi’an Jiaotong University,Xi’an,China 10.Department of Biochemistry,School of Medicine,Southern University of Science and Technology,Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research,Shenzhen Key Laboratory of Cell Microenvironment,Shenzhen,China 11.Institute of Molecular and Cell Biology,Agency for Science,Technology,and Research,Singapore,Singapore 12.Center for Neuro-Metabolism and Regeneration Research,Guangzhou Regenerative Medicine and Health Guangdong Laboratory,Guangzhou,China |
| 第一作者单位 | 生命科学学院 |
| 通讯作者单位 | 生命科学学院 |
| 第一作者的第一单位 | 生命科学学院 |
| 推荐引用方式 GB/T 7714 |
Zhang，Xiaozhe,Li，Na,Zhang，Jun,et al. 5-IP7 is a GPCR messenger mediating neural control of synaptotagmin-dependent insulin exocytosis and glucose homeostasis[J]. Nature Metabolism,2021,3:1400-1414.
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| APA |
Zhang，Xiaozhe.,Li，Na.,Zhang，Jun.,Zhang，Yanshen.,Yang，Xiaoli.,...&Rao，Feng.(2021).5-IP7 is a GPCR messenger mediating neural control of synaptotagmin-dependent insulin exocytosis and glucose homeostasis.Nature Metabolism,3,1400-1414.
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| MLA |
Zhang，Xiaozhe,et al."5-IP7 is a GPCR messenger mediating neural control of synaptotagmin-dependent insulin exocytosis and glucose homeostasis".Nature Metabolism 3(2021):1400-1414.
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| 条目包含的文件 | ||||||
| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | 操作 | |
| 35. Nat. Meta.5-IP7_（11486KB） | -- | -- | 限制开放 | -- | ||
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