Rapid regulation of endoplasmic reticulum dynamics in dendritic spines by NMDA receptor activation

被引:0
作者
Ai Na Ng
Andrew J Doherty
Paul J Lombroso
Nigel J Emptage
Graham L Collingridge
机构
[1] School of Physiology and Pharmacology,Centre for Synaptic Plasticity
[2] University of Bristol,Child Study Centre and Departments of Neurobiology and Psychiatry
[3] Yale University,Department of Pharmacology
[4] University of Oxford,undefined
来源
Molecular Brain | / 7卷
关键词
NMDA; Tyrosine phosphatase STEP; Endoplasmic reticulum; Dendritic spine; Hippocampus; Live cell imaging; Primary culture;
D O I
暂无
中图分类号
学科分类号
摘要
Endoplasmic reticulum (ER) is motile within dendritic spines, but the mechanisms underlying its regulation are poorly understood. To address this issue, we have simultaneously imaged morphology and ER content of dendritic spines in cultured dissociated mouse hippocampal neurons. Over a 10 min period, spines were highly dynamic, with spines both increasing and decreasing in volume. ER was present in approximately 50% of spines and was also highly dynamic, with a net increase over this period of time. Inhibition of the endogenous activation of NMDA receptors resulted in a reduction in ER growth. Conversely, augmentation of the synaptic activation of NMDA receptors, by elimination of striatal-enriched protein tyrosine phosphatase (STEP), resulted in enhanced ER growth. Therefore, NMDA receptors rapidly regulate spine ER dynamics.
引用
收藏
相关论文
共 157 条
[11]  
Grant SGN(2004)Bidirectional activity-dependent morphological plasticity in hippocampal neurons Neuron 44 759-E312
[12]  
Verkhratsky A(2013)Synapse-specific and size-dependent mechanisms of spine structural plasticity accompanying synaptic weakening Proc Natl Acad Sci 110 E305-2856
[13]  
Brünig I(2006)Regulation of NMDA receptor trafficking and function by striatal-enriched tyrosine phosphatase (STEP) Eur J Neurosci 23 2847-87
[14]  
Kaech S(2012)Therapeutic implications for striatal-enriched protein tyrosine phosphatase (STEP) in neuropsychiatric disorders Pharmacol Rev 64 65-42
[15]  
Brinkhaus H(2003)NMDA-mediated activation of the tyrosine phosphatase STEP regulates the duration of ERK signaling Nat Neurosci 6 34-138
[16]  
Oertner TG(2002)Tyrosine phosphatase STEP is a tonic brake on induction of long-term potentiation Neuron 34 127-1725
[17]  
Matus A(1996)Ca(2+)-independent reduction of N-methyl-D-aspartate channel activity by protein tyrosine phosphatase Proc Natl Acad Sci U S A 93 1721-678
[18]  
De Roo M(1997)NMDA channel regulation by channel-associated protein tyrosine kinase Src Science 275 674-1968
[19]  
Klauser P(2008)The tyrosine phosphatase STEP mediates AMPA receptor endocytosis after metabotropic glutamate receptor stimulation J Neurosci 28 10561-543
[20]  
Muller D(1992)4-Amido-2-carboxytetrahydroquinolines. Structure-activity relationships for antagonism at the glycine site of the NMDA receptor J Med Chem 35 1954-2510