title: A novel phosphorylation site of N-methyl-D-aspartate receptor GluN2B at S1284 is regulated by Cdk5 in neuronal ischemia.
abstract: N-methyl-D-aspartate receptors (NMDARs) are a key player in synaptic and several neurological diseases, such as stroke. Phosphorylation of NMDAR subunits at their cytoplasmic carboxyl termini has been considered to be an important mechanism to regulate the receptor function. Cyclin-dependent kinase 5 (Cdk5) has been demonstrated to be responsible for regulating phosphorylation and function of NMDARs. Besides, it is also suggested that Cdk5 is involved in ischemic insult. In the present study, we showed that GluN2B subunit serine 1284 at its cytoplasmic carboxyl termini was regulated by Cdk5 in neuronal ischemia. Interestingly, both oxygen glucose deprivation (OGD) in cultured hippocampal neurons and transient global ischemia in mice induce dramatic changes in the phosphorylated level of GluN2B at S1284. However, no significant changes in the phosphorylation of this site are found neither in chemical LTP stimulation in cultured hippocampal neurons nor fear conditioning in adult mice. Taken together, our study identified NMDAR GluN2B S1284 as a novel phosphorylation site regulated by Cdk5 with implication in neuronal ischemia.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Physiology, Zhejiang Medical College, Hangzhou, Zhejiang 310053, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Ai
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Jie-jie
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. Electronic address: luojianhong@zju.edu.cn.
authors.forename: Jian-hong
authors.initials: JH
authors.lastname: Luo
mesh_terms: D000818:Animals; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000166:cytology; D000860:Hypoxia / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology; D057907:Post-Synaptic Density / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*
chemical_list: D000697:Central Nervous System Stimulants; D051360:Cyclin-Dependent Kinase 5; D005947:Glucose; D010852:Picrotoxin; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; C121001:NR2B NMDA receptor
keywords: Cdk5; GluN2B; Ischemia; LTP; NMDA receptor; S1284