Ablation of TFR1 in Purkinje Cells Inhibits mGlu1 Trafficking and Impairs Motor Coordination, But Not Autistic-Like Behaviors

doi:10.1523/JNEUROSCI.1223-17.2017

	Ablation of TFR1 in Purkinje Cells Inhibits mGlu1 Trafficking and Impairs Motor Coordination, But Not Autistic-Like Behaviors
	Zhou, Jia-Huan 1; Wang, Xin-Tai 1; Zhou, Liang 1; Zhou, Lin 1; Xu, Fang-Xiao 1; Su, Li-Da 2; Wang, Hao 1; Jia, Fan 6; Xu, Fu-Qiang 6; Chen, Gui-Quan 3
刊名	JOURNAL OF NEUROSCIENCE
	2017-11-22
卷号	37 期号:47 页码:11335-11352
关键词	Autism Metabotropic Glutamate Receptor Motor Coordination Purkinje Cell Trafficking Transferrin Receptor
ISSN号	0270-6474
DOI	10.1523/JNEUROSCI.1223-17.2017
文献子类	Article
英文摘要	Group 1 metabotropic glutamate receptors (mGlu1/5s) are critical to synapse formation and participate in synaptic LTP and LTD in the brain. mGlu1/5 signaling alterations have been documented in cognitive impairment, neurodegenerative disorders, and psychiatric diseases, but underlying mechanisms for its modulation are not clear. Here, we report that transferrin receptor 1 (TFR1), a transmembrane protein of the clathrin complex, modulates the trafficking of mGlu1 in cerebellar Purkinje cells (PCs) from male mice. Weshow that conditional knock-out of TFR1 in PCs does not affect the cytoarchitecture of PCs, but reduces mGlu1 expression at synapses. This regulation by TFR1acts inconcert with that by Rab8 and Rab11, which modulate the internalization and recycling ofmGlu1, respectively. TFR1 canbind to Rab proteins and facilitate their expression at synapses. PC ablation of TFR1 inhibits parallel fiber-PC LTD, whereas parallel fiber-LTP and PC intrinsic excitability are not affected. Finally, we demonstrate that PC ablation of TFR1 impairs motor coordination, but does not affect social behaviors in mice. Together, these findings underscore the importance of TFR1 in regulating mGlu1 trafficking and suggest that mGlu1-and mGlu1-dependent parallel fiber-LTD are associated with regulation of motor coordination, but not autistic behaviors.
WOS关键词	LONG-TERM DEPRESSION ; METABOTROPIC GLUTAMATE RECEPTORS ; AGONIST-INDUCED INTERNALIZATION ; CENTRAL-NERVOUS-SYSTEM ; TRANSFERRIN RECEPTOR ; MUTANT MICE ; CEREBELLAR DYSFUNCTION ; SYNAPTIC PLASTICITY ; SOCIAL-BEHAVIOR ; RODENT MODELS
WOS研究方向	Neurosciences & Neurology
语种	英语
出版者	SOC NEUROSCIENCE
WOS记录号	WOS:000416595200006
资助机构	National Natural Science Foundation of China(81625006 ; National Natural Science Foundation of China(81625006 ; Natural Science Foundation of Zhejiang Province(Z15C090001 ; Natural Science Foundation of Zhejiang Province(Z15C090001 ; Chinese Ministry of Education (Project 111 Program)(B13026) ; Chinese Ministry of Education (Project 111 Program)(B13026) ; Zhejiang Province Medical and Health Research Foundation(2017200463) ; Zhejiang Province Medical and Health Research Foundation(2017200463) ; Dutch Organization for Medical Sciences and Life Sciences ; Dutch Organization for Medical Sciences and Life Sciences ; ERC-adv of the European Union ; ERC-adv of the European Union ; ERC-POC of the European Union ; ERC-POC of the European Union ; 31471024 ; 31471024 ; LY15C090001) ; LY15C090001) ; 31571051) ; 31571051) ; National Natural Science Foundation of China(81625006 ; National Natural Science Foundation of China(81625006 ; Natural Science Foundation of Zhejiang Province(Z15C090001 ; Natural Science Foundation of Zhejiang Province(Z15C090001 ; Chinese Ministry of Education (Project 111 Program)(B13026) ; Chinese Ministry of Education (Project 111 Program)(B13026) ; Zhejiang Province Medical and Health Research Foundation(2017200463) ; Zhejiang Province Medical and Health Research Foundation(2017200463) ; Dutch Organization for Medical Sciences and Life Sciences ; Dutch Organization for Medical Sciences and Life Sciences ; ERC-adv of the European Union ; ERC-adv of the European Union ; ERC-POC of the European Union ; ERC-POC of the European Union ; 31471024 ; 31471024 ; LY15C090001) ; LY15C090001) ; 31571051) ; 31571051) ; National Natural Science Foundation of China(81625006 ; National Natural Science Foundation of China(81625006 ; Natural Science Foundation of Zhejiang Province(Z15C090001 ; Natural Science Foundation of Zhejiang Province(Z15C090001 ; Chinese Ministry of Education (Project 111 Program)(B13026) ; Chinese Ministry of Education (Project 111 Program)(B13026) ; Zhejiang Province Medical and Health Research Foundation(2017200463) ; Zhejiang Province Medical and Health Research Foundation(2017200463) ; Dutch Organization for Medical Sciences and Life Sciences ; Dutch Organization for Medical Sciences and Life Sciences ; ERC-adv of the European Union ; ERC-adv of the European Union ; ERC-POC of the European Union ; ERC-POC of the European Union ; 31471024 ; 31471024 ; LY15C090001) ; LY15C090001) ; 31571051) ; 31571051) ; National Natural Science Foundation of China(81625006 ; National Natural Science Foundation of China(81625006 ; Natural Science Foundation of Zhejiang Province(Z15C090001 ; Natural Science Foundation of Zhejiang Province(Z15C090001 ; Chinese Ministry of Education (Project 111 Program)(B13026) ; Chinese Ministry of Education (Project 111 Program)(B13026) ; Zhejiang Province Medical and Health Research Foundation(2017200463) ; Zhejiang Province Medical and Health Research Foundation(2017200463) ; Dutch Organization for Medical Sciences and Life Sciences ; Dutch Organization for Medical Sciences and Life Sciences ; ERC-adv of the European Union ; ERC-adv of the European Union ; ERC-POC of the European Union ; ERC-POC of the European Union ; 31471024 ; 31471024 ; LY15C090001) ; LY15C090001) ; 31571051) ; 31571051)
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/12734]
专题	中国科学院武汉物理与数学研究所
通讯作者	De Zeeuw, Chris I.; Shen, Ying
作者单位	1.Zhejiang Univ, Sch Med, Minist Hlth, Dept Neurobiol,Key Lab Med Neurobiol, 866 Yu Hang Tang Rd, Hangzhou 310058, Zhejiang, Peoples R China 2.Zhejiang Univ, Sch Med, Affiliated Hosp 2, Neurosci Care Unit, Hangzhou 310009, Zhejiang, Peoples R China 3.Nanjing Univ, Model Anim Res Ctr, MOE Key Lab Model Anim Dis Study, State Key Lab Pharmaceut Biotechnol, Nanjing 210032, Jiangsu, Peoples R China 4.Royal Dutch Acad Arts & Sci, Netherlands Inst Neurosci, NL-1105 BA Amsterdam, Netherlands 5.Erasmus MC, Dept Neurosci, NL-3000 CA Rotterdam, Netherlands 6.Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan 430071, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Zhou, Jia-Huan,Wang, Xin-Tai,Zhou, Liang,et al. Ablation of TFR1 in Purkinje Cells Inhibits mGlu1 Trafficking and Impairs Motor Coordination, But Not Autistic-Like Behaviors[J]. JOURNAL OF NEUROSCIENCE,2017,37(47):11335-11352.
APA	Zhou, Jia-Huan.,Wang, Xin-Tai.,Zhou, Liang.,Zhou, Lin.,Xu, Fang-Xiao.,...&Shen, Ying.(2017).Ablation of TFR1 in Purkinje Cells Inhibits mGlu1 Trafficking and Impairs Motor Coordination, But Not Autistic-Like Behaviors.JOURNAL OF NEUROSCIENCE,37(47),11335-11352.
MLA	Zhou, Jia-Huan,et al."Ablation of TFR1 in Purkinje Cells Inhibits mGlu1 Trafficking and Impairs Motor Coordination, But Not Autistic-Like Behaviors".JOURNAL OF NEUROSCIENCE 37.47(2017):11335-11352.