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Trafficking and Regulation of the NMDA Receptor Subunit NR2C

NMDA 受体亚基 NR2C 的贩运和调控

基本信息

批准号：
8321558
负责人：
BO-SHIUN CHEN
金额：
$ 24.52万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8321558
关键词：
Address Alzheimer&apos s Disease Behavioral Binding Proteins Biochemical Biochemistry Biological Models Biology Brain region Calcium Cell Survival Cell membrane Cells Cellular biology Cerebellum Cerebral Ischemia Cessation of life Chimera organism Cyclic AMP-Dependent Protein Kinases Development Disease Distal Dominant-Negative Mutation Endocytosis Exhibits Glucose Goals Hela Cells Hippocampus (Brain)In Vitro Instruction Insulin Integral Membrane Protein Ischemia Knockout Mice Link Magnesium Mediating Mediator of activation protein Mental disorders Metabolic Modeling Molecular Monitor N-Methyl-D-Aspartate Receptors NMDA receptor antagonist NR1 gene Neurites Neurons Oxygen Pathway interactions Pattern Phenotype Phosphorylation Phosphorylation Site Phosphotransferases Physiological Play Postsynaptic Membrane Process Property Protein Dephosphorylation Protein Kinase Protein Kinase C Protein phosphatase Proteins Regulation Reporter Research Role Schizophrenia Serine Serine/Threonine Phosphorylation Signal Pathway Signal Transduction Site Sorting - Cell Movement Subfamily lentivirinae Surface Synapses Synaptic Transmission Synaptic plasticity Testing Thalamic structure The Sun Threonine Phosphorylation Site Work base deprivation design excitotoxicity extracellular granule cell inhibitor/antagonist insight knock-down magnesium ion nervous system disorder neuron development neuronal survival neurotransmission novel olfactory bulb overexpression receptor receptor binding receptor function response therapeutic development tool trafficking voltage

项目摘要

The long-term goal of my research is to understand the molecular mechanism by which NMDA receptors are regulated to modulate the strength of synaptic transmission, and to use this information for development of therapeutic strategies to treat neurological and psychiatric diseases. Efficient trafficking of NMDA receptors to synaptic sites is critical for normal excitatory neurotransmission. Intracellular domains of NMDA receptors bind to cytosolic proteins and serve as substrates for protein kinases, thereby regulating synaptic expression and function. NMDA receptors are made up of distinct subunits with unique expression throughout the CNS and with specific function and properties. This proposal addresses the role of the NMDA receptor subunit NR2C in NMDA receptor regulation and trafficking. NR2C confers unique properties on NMDA receptors producing channels relatively insensitive to the voltage-dependent block by magnesium ions. NR2C is highly enriched in cerebellum, thalamus and olfactory bulb. Thus the mechanisms regulating NR2C surface expression and function are likely to be critical in defining NMDA receptor properties in these brain regions. I will use a combination of molcular biology, biochemistry and cell biology to characterize the regulation of NR2C surface expression and the function of NR2C-containing NMDA receptors. The goals are to: 1) Define the role of NR2C-containing NMDA receptors in neuronal survival and elucidate its signaling pathway. 2) Define the role of NR2C phosphorylation in the regulation and trafficking of NMDA receptors. 3) Define the molecular mechanisms underlying subunit-specific regulation of NMDA receptors in cerebellum. The successful completion of these studies is expected to provide the first detailed examination of the regulation of NR2C and provide insight into the funcitonal significance of NR2C-containing receptors for cerebellar funciton.

我研究的长期目标是了解NMDA受体的分子机制

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Regulation of SAP102 Synaptic Targeting by Phosphorylation.

DOI：
10.1007/s12035-017-0836-4
发表时间：
2018-08
期刊：
Molecular neurobiology
影响因子：
5.1
作者：
Wei Z;Wu G;Chen BS
通讯作者：
Chen BS

NMDA receptor-dependent regulation of dendritic spine morphology by SAP102 splice variants.

DOI：
10.1523/jneurosci.1034-10.2011
发表时间：
2011-01-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Chen BS;Thomas EV;Sanz-Clemente A;Roche KW
通讯作者：
Roche KW

NMDA receptor signaling: death or survival?