Postsynaptic protein mobility in dendritic spines: Long-term regulation by synaptic NMDA receptor activation

Kamal Sharma; Dan K. Fong; Ann Marie Craig

doi:10.1016/j.mcn.2006.01.010

Postsynaptic protein mobility in dendritic spines: Long-term regulation by synaptic NMDA receptor activation

Kamal Sharma, Dan K. Fong, Ann Marie Craig

Research output: Contribution to journal › Article › peer-review

120 Scopus citations

Abstract

Reorganization of molecular components represents a cellular mechanism for synaptic plasticity. Dendritic spines, major sites for glutamatergic synapses, compartmentalize dynamic changes in molecular composition. Here, we use fluorescence recovery after photobleaching (FRAP) in cultured hippocampal neurons to show that spine proteins undergo continual exchange with extra-spine pools. Each spine component has a distinctive mobility: calcium/calmodulin activated protein kinase CaMKIIα > GluR1 AMPA glutamate receptor > PSD-95 scaffolding protein > NR1 NMDA glutamate receptor. Stimulation of synaptic NMDA receptors by a protocol that induces chemical LTP resulted in a long-lasting reduction in the mobility of spine CaMKIIα and an increased mobile fraction but slower kinetics for spine GluR1. Stimulation also increased the resistance of postsynaptic CaMKIIα to detergent extraction. These results suggest long-lasting changes in affinity of protein-protein interactions and/or ongoing alterations in exo/endocytosis. Such lasting changes in protein mobility may contribute to maintaining alterations in synaptic efficacy.

Original language	English (US)
Pages (from-to)	702-712
Number of pages	11
Journal	Molecular and Cellular Neuroscience
Volume	31
Issue number	4
DOIs	https://doi.org/10.1016/j.mcn.2006.01.010
State	Published - Apr 2006
Externally published	Yes

Keywords

CaMKII
FRAP
GluR1
Hippocampal
LTP
NR1
PSD-95

ASJC Scopus subject areas

Molecular Biology
Cellular and Molecular Neuroscience
Cell Biology

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10.1016/j.mcn.2006.01.010

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title = "Postsynaptic protein mobility in dendritic spines: Long-term regulation by synaptic NMDA receptor activation",

abstract = "Reorganization of molecular components represents a cellular mechanism for synaptic plasticity. Dendritic spines, major sites for glutamatergic synapses, compartmentalize dynamic changes in molecular composition. Here, we use fluorescence recovery after photobleaching (FRAP) in cultured hippocampal neurons to show that spine proteins undergo continual exchange with extra-spine pools. Each spine component has a distinctive mobility: calcium/calmodulin activated protein kinase CaMKIIα > GluR1 AMPA glutamate receptor > PSD-95 scaffolding protein > NR1 NMDA glutamate receptor. Stimulation of synaptic NMDA receptors by a protocol that induces chemical LTP resulted in a long-lasting reduction in the mobility of spine CaMKIIα and an increased mobile fraction but slower kinetics for spine GluR1. Stimulation also increased the resistance of postsynaptic CaMKIIα to detergent extraction. These results suggest long-lasting changes in affinity of protein-protein interactions and/or ongoing alterations in exo/endocytosis. Such lasting changes in protein mobility may contribute to maintaining alterations in synaptic efficacy.",

keywords = "CaMKII, FRAP, GluR1, Hippocampal, LTP, NR1, PSD-95",

author = "Kamal Sharma and Fong, {Dan K.} and Craig, {Ann Marie}",

note = "Funding Information: We thank Huaiyang Wu and Xiling Zhou for excellent preparation of neuron cultures, Dr. Kimberly J. Harms, Ji-Young Kim, and Chenghua Wu for generating fusion protein constructs, and Dr. Rachel Wong for expert assistance with imaging. This work was supported by NIH NS33184, CIHR MOP69096 and MSFHR Establishment grants, and Canada Research Chair (AMC). ",

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T2 - Long-term regulation by synaptic NMDA receptor activation

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AU - Craig, Ann Marie

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N2 - Reorganization of molecular components represents a cellular mechanism for synaptic plasticity. Dendritic spines, major sites for glutamatergic synapses, compartmentalize dynamic changes in molecular composition. Here, we use fluorescence recovery after photobleaching (FRAP) in cultured hippocampal neurons to show that spine proteins undergo continual exchange with extra-spine pools. Each spine component has a distinctive mobility: calcium/calmodulin activated protein kinase CaMKIIα > GluR1 AMPA glutamate receptor > PSD-95 scaffolding protein > NR1 NMDA glutamate receptor. Stimulation of synaptic NMDA receptors by a protocol that induces chemical LTP resulted in a long-lasting reduction in the mobility of spine CaMKIIα and an increased mobile fraction but slower kinetics for spine GluR1. Stimulation also increased the resistance of postsynaptic CaMKIIα to detergent extraction. These results suggest long-lasting changes in affinity of protein-protein interactions and/or ongoing alterations in exo/endocytosis. Such lasting changes in protein mobility may contribute to maintaining alterations in synaptic efficacy.

AB - Reorganization of molecular components represents a cellular mechanism for synaptic plasticity. Dendritic spines, major sites for glutamatergic synapses, compartmentalize dynamic changes in molecular composition. Here, we use fluorescence recovery after photobleaching (FRAP) in cultured hippocampal neurons to show that spine proteins undergo continual exchange with extra-spine pools. Each spine component has a distinctive mobility: calcium/calmodulin activated protein kinase CaMKIIα > GluR1 AMPA glutamate receptor > PSD-95 scaffolding protein > NR1 NMDA glutamate receptor. Stimulation of synaptic NMDA receptors by a protocol that induces chemical LTP resulted in a long-lasting reduction in the mobility of spine CaMKIIα and an increased mobile fraction but slower kinetics for spine GluR1. Stimulation also increased the resistance of postsynaptic CaMKIIα to detergent extraction. These results suggest long-lasting changes in affinity of protein-protein interactions and/or ongoing alterations in exo/endocytosis. Such lasting changes in protein mobility may contribute to maintaining alterations in synaptic efficacy.

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Postsynaptic protein mobility in dendritic spines: Long-term regulation by synaptic NMDA receptor activation

Abstract

Keywords

ASJC Scopus subject areas

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