CASK modulates the assembly and function of the Mint1/Munc18-1 complex to regulate insulin secretion

doi:10.1038/s41421-020-00216-3

	CASK modulates the assembly and function of the Mint1/Munc18-1 complex to regulate insulin secretion
	Zhang, Zhe 1; Li, Wei 2; Yang, Guang 1,3; Lu, Xuefeng 1; Qi, Xin 2,4; Wang, Shuting 1,4; Cao, Can 1; Zhang, Peng 1; Ren, Jinqi 2; Zhao, Jiaxu 1; Zhang, Junyi 1; Hong, Sheng5 ; Tan, Yan 1; Burchfield, James 3; Yu, Yang 6; Xu, Tao 2; Yao, Xuebiao 7; James, David 3,8; Feng, Wei 2,4; Chen, Zhengjun1,5
	2020-12-15
发表期刊	CELL DISCOVERY
卷号	6 期号:1
发表状态	已发表
DOI	10.1038/s41421-020-00216-3
摘要	Calcium/calmodulin-dependent protein serine kinase (CASK) is a key player in vesicle transport and release in neurons. However, its precise role, particularly in nonneuronal systems, is incompletely understood. We report that CASK functions as an important regulator of insulin secretion. CASK depletion in mouse islets/beta cells substantially reduces insulin secretion and vesicle docking/fusion. CASK forms a ternary complex with Mint1 and Munc18-1, and this event is regulated by glucose stimulation in beta cells. The crystal structure of the CASK/Mint1 complex demonstrates that Mint1 exhibits a unique "whip"-like structure that wraps tightly around the CASK-CaMK domain, which contains dual hydrophobic interaction sites. When triggered by CASK binding, Mint1 modulates the assembly of the complex. Further investigation revealed that CASK-Mint1 binding is critical for ternary complex formation, thereby controlling Munc18-1 membrane localization and insulin secretion. Our work illustrates the distinctive molecular basis underlying CASK/Mint1/Munc18-1 complex formation and reveals the importance of the CASK-Mint1-Munc18 signaling axis in insulin secretion.
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收录类别	SCI ; SCIE
语种	英语
资助项目	National Key R&D Program of China[2017YFA0503501] ; Strategic Priority Research Program of CAS[XDB37020302] ; National Natural Science Foundation of China[31430055][31770786][31829001][31971160][31190062][30730055][31170723] ; National Key Basic Research Program of China[2012CB945001][2011CB910601]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000598764200001
出版者	SPRINGERNATURE
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/124914
专题	生命科学与技术学院_硕士生生命科学与技术学院_特聘教授组_陈正军组
通讯作者	Feng, Wei; Chen, Zhengjun
作者单位	1.Chinese Acad Sci, State Key Lab Cell Biol, CAS Ctr Excellence Mol Cell Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Natl Lab Biomacromol, CAS Ctr Excellence Biomacromol, Inst Biophys, Beijing 100101, Peoples R China 3.Univ Sydney, Sch Life & Environm Sci, Charles Perkins Ctr, Sydney, NSW 2006, Australia 4.Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai, Shanghai 200031, Peoples R China 7.Univ Sci & Technol China, Hefei Natl Lab Phys Sci Nanoscale, Anhui Key Lab Cellular Dynam & Chem Biol, Hefei 230026, Anhui, Peoples R China 8.Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Zhang, Zhe,Li, Wei,Yang, Guang,et al. CASK modulates the assembly and function of the Mint1/Munc18-1 complex to regulate insulin secretion[J]. CELL DISCOVERY,2020,6(1).
APA	Zhang, Zhe.,Li, Wei.,Yang, Guang.,Lu, Xuefeng.,Qi, Xin.,...&Chen, Zhengjun.(2020).CASK modulates the assembly and function of the Mint1/Munc18-1 complex to regulate insulin secretion.CELL DISCOVERY,6(1).
MLA	Zhang, Zhe,et al."CASK modulates the assembly and function of the Mint1/Munc18-1 complex to regulate insulin secretion".CELL DISCOVERY 6.1(2020).