TMCO1 Is an ER Ca2+ Load-Activated Ca2+ Channel

doi:10.1016/j.cell.2016.04.051

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	TMCO1 Is an ER Ca2+ Load-Activated Ca2+ Channel
	Wang, Qiao-Chu 8; Zheng, Qiaoxia 8; Tan, Haiyan 5,6; Zhang, Bing 7; Li, Xiaoling 8; Yang, Yuxiu 7; Yu, Jie 1; Liu, Yang 2; Chai, Hao 7; Wang, Xi 8
刊名	CELL
	2016-06-02
卷号	165 期号:6 页码:1454-1466
ISSN号	0092-8674
DOI	10.1016/j.cell.2016.04.051
文献子类	Article
英文摘要	Maintaining homeostasis of Ca2+ stores in the endoplasmic reticulum (ER) is crucial for proper Ca2+ signaling and key cellular functions. The Ca2+-release-activated Ca2+ (CRAC) channel is responsible for Ca2+ influx and refilling after store depletion, but how cells cope with excess Ca2+ when ER stores are overloaded is unclear. We show that TMCO1 is an ER transmembrane protein that actively prevents Ca2+ stores from overfilling, acting as what we term a "Ca2+ load-activated Ca2+ channel" or "CLAC" channel. TMCO1 undergoes reversible homotetramerization in response to ER Ca2+ overloading and disassembly upon Ca2+ depletion and forms a Ca2+-selective ion channel on giant liposomes. TMCO1 knockout mice reproduce the main clinical features of human cerebrofaciothoracic (CFT) dysplasia spectrum, a developmental disorder linked to TMCO1 dysfunction, and exhibit severe mishandling of ER Ca2+ in cells. Our findings indicate that TMCO1 provides a protective mechanism to prevent overfilling of ER stores with Ca2+ ions.
资助项目	National Basic Research Program of China[2012CB944702] ; National Basic Research Program of China[NSFC 81371415] ; National Basic Research Program of China[91519324] ; National Basic Research Program of China[31570816] ; National Basic Research Program of China[31401151] ; National Basic Research Program of China[81300982] ; Ohio Research Scholars Program[00000000] ; Faculty Research and Development Program of Cleveland State University[00000000] ; [2013CB91060101] ; [3137106601] ; [3117101101] ; [2012ZX09301] ; [2011CB910502] ; [2012CB911101] ; [NSFC 31030020] ; [31170679] ; [2013CB945003] ; [31471331] ; [XDB14030302]
WOS关键词	ENDOPLASMIC-RETICULUM STRESS ; OPERATED CALCIUM-ENTRY ; PLASMA-MEMBRANE ; CRAC CHANNEL ; INOSITOL TRISPHOSPHATE ; ALZHEIMERS-DISEASE ; STORE DEPLETION ; STIM1 ; ORAI1 ; SENSOR
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000377045400018
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276009]
专题	药理学第二研究室
通讯作者	Zhou, Aimin; Tang, Tie-Shan
作者单位	1.Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Sch Life Sci, Ministry Educ,Key Lab Prot Sci,Tsinghua Peking Jo, Beijing 100084, Peoples R China; 2.Chinese Acad Sci, Beijing Inst Genom, China Gastrointestinal Canc Res Ctr, Key Lab Genom & Precis Med, Beijing 100101, Peoples R China; 3.Ctr Special Needs Children, DDC Clin, Middlefield, OH 44062 USA; 4.Case Western Reserve Univ, Dept Otolaryngol HNS, Cleveland, OH 44106 USA 5.Cleveland State Univ, Dept Chem, Cleveland, OH 44115 USA; 6.Cleveland State Univ, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA; 7.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 8.Chinese Acad Sci, Univ Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing 100101, Peoples R China;
推荐引用方式 GB/T 7714	Wang, Qiao-Chu,Zheng, Qiaoxia,Tan, Haiyan,et al. TMCO1 Is an ER Ca2+ Load-Activated Ca2+ Channel[J]. CELL,2016,165(6):1454-1466.
APA	Wang, Qiao-Chu.,Zheng, Qiaoxia.,Tan, Haiyan.,Zhang, Bing.,Li, Xiaoling.,...&Tang, Tie-Shan.(2016).TMCO1 Is an ER Ca2+ Load-Activated Ca2+ Channel.CELL,165(6),1454-1466.
MLA	Wang, Qiao-Chu,et al."TMCO1 Is an ER Ca2+ Load-Activated Ca2+ Channel".CELL 165.6(2016):1454-1466.