title: Transferrin Receptor Controls AMPA Receptor Trafficking Efficiency and Synaptic Plasticity.
abstract: Transferrin receptor (TFR) is an important iron transporter regulating iron homeostasis and has long been used as a marker for clathrin mediated endocytosis. However, little is known about its additional function other than iron transport in the development of central nervous system (CNS). Here we demonstrate that TFR functions as a regulator to control AMPA receptor trafficking efficiency and synaptic plasticity. The conditional knockout (KO) of TFR in neural progenitor cells causes mice to develop progressive epileptic seizure, and dramatically reduces basal synaptic transmission and long-term potentiation (LTP). We further demonstrate that TFR KO remarkably reduces the binding efficiency of GluR2 to AP2 and subsequently decreases AMPA receptor endocytosis and recycling. Thus, our study reveals that TFR functions as a novel regulator to control AMPA trafficking efficiency and synaptic plasticity.
authors.affiliation: West China Developmental &Stem Cell Institute, West China Second Hospital, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China.|Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative Biology, Institute of Biomedicine &Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.|SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine &Advanced Institute of Translational Medicine, Shanghai 200123, China.|ATCG Corp., BioBay, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.affiliation: West China Developmental &Stem Cell Institute, West China Second Hospital, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, China.|Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative Biology, Institute of Biomedicine &Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.|SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine &Advanced Institute of Translational Medicine, Shanghai 200123, China.|ATCG Corp., BioBay, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China.
authors.forename: Run
authors.initials: R
authors.lastname: Lei
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province,Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province,Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Wang
authors.affiliation: Department of Nutrition, School of Public Health, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Nutrition, School of Public Health, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Peng
authors.initials: P
authors.lastname: An
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative Biology, Institute of Biomedicine &Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: Jianchao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine &Advanced Institute of Translational Medicine, Shanghai 200123, China.|ATCG Corp., BioBay, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China.
authors.forename: Minyan
authors.initials: M
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Cell Biology &Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Nutrition, School of Public Health, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Fudi
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province,Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Shenzhen Key Laboratory for Molecular Biology of Neural Development, Laboratory of Developmental and Regenerative Biology, Institute of Biomedicine &Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, China.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Li
authors.affiliation: SARITEX Center for Stem Cell Engineering Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine &Advanced Institute of Translational Medicine, Shanghai 200123, China.|ATCG Corp., BioBay, Suzhou Industrial Park, Suzhou, Jiangsu 215123, China.
authors.forename: Huashun
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D017774:Long-Term Potentiation; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D018091:Receptors, AMPA; D011990:Receptors, Transferrin; C104722:glutamate receptor ionotropic, AMPA 2