Driving AMPA Receptors into Synapses by LTP and CaMKII: Requirement for GluR1 and PDZ Domain Interaction
SciencePublished 24 March 2000
Yasunori Hayashi, Song-Hai Shi, José A. Esteban, Antonella Piccini, Jean Christophe Poncer, Roberto Malinow
Citations1,525
SJR quartileQ1
SJR score10.42
SNIP6.62
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Results show that LTP and CaMKII activity drive AMPA-Rs to synapses by a mechanism that requires the association between GluR1 and a PDZ domain protein.
Abstract
To elucidate mechanisms that control and execute activity-dependent synaptic plasticity, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPA-Rs) with an electrophysiological tag were expressed in rat hippocampal neurons. Long-term potentiation (LTP) or increased activity of the calcium/calmodulin-dependent protein kinase II (CaMKII) induced delivery of tagged AMPA-Rs into synapses. This effect was not diminished by mutating the CaMKII phosphorylation site on the GluR1 AMPA-R subunit, but was blocked by mutating a predicted PDZ domain interaction site. These results show that LTP and CaMKII activity drive AMPA-Rs to synapses by a mechanism that requires the association between GluR1 and a PDZ domain protein.
Keywords
NeuroscienceBiochemistry, Genetics and Molecular Biology
NatureA synaptic model of memory: long-term potentiation in the hippocampus
11,542 Citations1993T.V.P. Bliss, Graham L. Collingridge
The best understood form of long-term potentiation is induced by the activation of the N-methyl-d-aspartate receptor complex, which allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and post Synaptic mechanisms to generate a persistent increase in synaptic strength.
ScienceDeficient Hippocampal Long-Term Potentiation in α-Calcium-Calmodulin Kinase II Mutant Mice
1,482 Citations1992Alcino J. Silva, Charles F. Stevens +2 more
W Whole cell recordings reveal that postsynaptic mechanisms, including N-methyl-D-aspartate (NMDA) receptor function, are intact and are therefore a suitable model for studying the relation between LTP and learning processes.
ScienceRecognition of Unique Carboxyl-Terminal Motifs by Distinct PDZ Domains
1,398 Citations1997Zhou Songyang, A. S. Fanning +8 more
On the basis of crystal structures of the PSD-95-3 PDZ domain, the specificities observed with the peptide library can be rationalized.
ScienceInhibition of Postsynaptic PKC or CaMKII Blocks Induction But Not Expression of LTP
1,330 Citations1989Roberto Malinow, Howard Schulman +1 more
Both postsynaptic PKC and CaMKII are required for the induction of LTP and a presynaptic protein kinase appears to be necessary for the expression of L TP, and both post synapses and protein kinases are sensitive to externally applied H-7.
ScienceRapid Spine Delivery and Redistribution of AMPA Receptors After Synaptic NMDA Receptor Activation
1,268 Citations1999Song‐Hai Shi, Yasunori Hayashi +5 more
Tetanic synaptic stimulation induced a rapid delivery of tagged receptors into dendritic spines as well as clusters in dendrites and may contribute to the enhanced AMPA receptor-mediated transmission observed during long-term potentiation and activity-dependent synaptic maturation.
ScienceRegulatory Phosphorylation of AMPA-Type Glutamate Receptors by CaM-KII During Long-Term Potentiation
1,044 Citations1997Andrés Barría, Dominique Müller +3 more
Induction of LTP increased the phosphorus-32 labeling of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA-Rs), which mediate rapid excitatory synaptic transmission and provides a postsynaptic molecular mechanism for synaptic plasticity.
NatureAn essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation
1,028 Citations1989Robert C. Malenka, Julie A. Kauer +5 more
It is found that intracellular injection into CA1 pyramidal cells of the protein kinase inhibitor H-7, or of the calmodulin antagonist calmidazolium, blocks LTP, and LTP is blocked by the injection of synthetic peptides that are potentCalmodulin antagonists and inhibit CaM-KII auto- and substrate phosphorylation.
NatureGRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors
867 Citations1997Hualing Dong, Richard O’Brien +4 more
Journal of NeuroscienceEvidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons
843 Citations1996RJ Wenthold, RS Petralia +2 more
The results show that AMPA receptor complexes with different subunit compositions are present in CA1/CA2 pyramidal neurons and suggest an additional mechanism to regulate receptor expression in neurons.
Proceedings of the National Academy of SciencesCa <sup>2+</sup> /calmodulin-kinase II enhances channel conductance of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors
841 Citations1999V. A. Derkach, Andrés Barría +1 more
Results indicate that CaM-KII can mediate plasticity at glutamatergic synapses by increasing single-channel conductance of existing functional AMPA-Rs or by recruiting new high-conductance-state AMPA -Rs.
ScienceStructural Determinants of Ion Flow Through Recombinant Glutamate Receptor Channels
822 Citations1991Todd A. Verdoorn, Nail Burnashev +3 more
The properties of heteromeric wild-type and mutant GluRs revealed that the dominance of GluR-B is due to the arginine residue in the TM2 region, and the steady-state current-voltage relations of glutamate- and kainate-induced currents through homomeric channels fell into two classes.
Annual Review of PhysiologyThe Multifunctional Calcium/Calmodulin-Dependent Protein Kinase: From Form to Function
814 Citations1995Andrew P. Braun, Howard Schulman
The regulation of cellular function by hormones and extracellular molecules, which bind to cell surface receptors, is initiated by signal transduction mech anisms at the plasma membrane that lead to the generation of intracellular signals, or second messengers.
NeuronNSF Binding to GluR2 Regulates Synaptic Transmission
546 Citations1998Atsushi Nishimune, John Isaac +7 more
A previously unsuspected direct interaction in the postsynaptic neuron between two major proteins involved in synaptic transmission is demonstrated and a rapid NSF-dependent modulation of AMPA receptor function is suggested.
NatureModulation of AMPA receptor unitary conductance by synaptic activity
525 Citations1998Tim A. Benke, Andreas Lüthi +2 more
It is shown that elementary channel properties can be rapidly modified by synaptic activity and provides an insight into one molecular mechanism by which glutamatergic synapses can alter their strength.
The Journal of PhysiologyAnalysis of excitatory synaptic action in pyramidal cells using whole‐cell recording from rat hippocampal slices.
495 Citations1990Shaul Hestrin, Roger A. Nicoll +2 more
These experiments provide a detailed description of the dual receptor mechanism operating at hippocampal excitatory synapses and an electrophysiological method for estimating the electrotonic distance of synaptic inputs.
Proceedings of the National Academy of SciencesCalcium/calmodulin-dependent kinase II and long-term potentiation enhance synaptic transmission by the same mechanism.
455 Citations1995Pierre‐Marie Lledo, Gregory O. Hjelmstad +4 more
It is indicated that CaM-K II alone is sufficient to augment synaptic strength and that this enhancement shares the same underlying mechanism as the enhancement observed with LTP.
Journal of Biological ChemistryPhosphorylation of the α-Amino-3-hydroxy-5-methylisoxazole4-propionic Acid Receptor GluR1 Subunit by Calcium/ Calmodulin-dependent Kinase II
440 Citations1997Andrew L. Mammen, Kimihiko Kameyama +2 more
Two-dimensional phosphopeptide mapping experiments indicate that Ser-831 is the major site of CaM kinase II phosphorylation on GLUR1 and demonstrate that GluR1 is multiply phosphorylated byprotein kinase A, protein kinase C, and CaM Kinase II in situ.
Journal of Biological ChemistrySAP97 Is Associated with the α-Amino-3-hydroxy-5-methylisoxazole-4-propionic Acid Receptor GluR1 Subunit
416 Citations1998A. Soren Leonard, Monika A. Davare +3 more
It is shown that SAP97, a SAP whose function at the synapse has been unclear, is associated with alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors and may be involved in localizing AMPA receptors at postsynaptic sites through its interaction with the GluR1 subunit.
NeuronInteraction of the N-Ethylmaleimide–Sensitive Factor with AMPA Receptors
401 Citations1998Insuk Song, Sunjeev K. Kamboj +4 more
Journal of Biological ChemistryIdentification of the Ca2+/Calmodulin-dependent Protein Kinase II Regulatory Phosphorylation Site in the α-Amino-3-hydroxyl-5-methyl4-isoxazole-propionate-type Glutamate Receptor
391 Citations1997Andrés Barría, V. A. Derkach +1 more
The Ser831 site is specific to GluR1, and CaM-KII did not phosphorylate or potentiate current in cells expressing GluGluR2, emphasizing the importance of the GLUR1 subunit in this regulatory mechanism.
Proceedings of the National Academy of SciencesEvidence that the major postsynaptic density protein is a component of a Ca2+/calmodulin-dependent protein kinase.
387 Citations1984PT Kelly, T L McGuinness +1 more
The present results indicate that the major postsynaptic density protein is a component of Ca2+/calmodulin-dependent protein kinase II.
ScienceStabilization of Dendritic Arbor Structure in Vivo by CaMKII
379 Citations1998Gang‐Yi Wu, Hollis T. Cline
Exogenous CaMKII activity limits dendritic growth and stabilizes dendrites, and it may act as an activity-dependent mediator of neuronal maturation.
Trends in Biochemical SciencesThe novel mechanism of initiation of picornavirus RNA translation
368 Citations1990Richard J. Jackson, Michael Howell +1 more
The initiation of translation of picornaviral RNAs takes place by an unusual mechanism whereby ribosomes bind directly to an internal site rather than scan the RNA from the 5'-end, which may be of relevance to the translation of some cellular mRNAs.
NeuronThe AMPA Receptor GluR2 C Terminus Can Mediate a Reversible, ATP-Dependent Interaction with NSF and α- and β-SNAPs
360 Citations1998Pavel Osten, Shalini Srivastava +9 more
This study demonstrates specific interaction of the GluR2 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit C-terminal peptide with an ATPase N-ethylmaleimide-sensitive fusion protein (NSF) and alpha- and beta-soluble NSF attachment proteins (SNAPs), as well as dendritic colocalization of these proteins.
SciencePotentiated Transmission and Prevention of Further LTP by Increased CaMKII activity in Postsynaptic Hippocampal Slice Neurons
333 Citations1994D. L. Pettit, Seth J. Perlman +1 more
It is suggested that postsynaptic CaMKII activity is necessary and sufficient to generate LTP.
Journal of Biological ChemistryDistinct forebrain and cerebellar isozymes of type II Ca2+/calmodulin-dependent protein kinase associate differently with the postsynaptic density fraction.
307 Citations1985Stephen G. Miller, Mary B. Kennedy
The alpha-subunit may play a role in anchoring Type II Ca2+/calmodulin-dependent protein kinase to postsynaptic densities in the cerebellar and forebrain regions.
NeuronSurface Expression of AMPA Receptors in Hippocampal Neurons Is Regulated by an NSF-Dependent Mechanism
302 Citations1999Jacques Noël, G. Ralph +6 more
It is shown that disruption of N-ethylmaleimide-sensitive fusion protein- (NSF-) GluR2 interaction by infusion into cultured hippocampal neurons of a blocking peptide caused a rapid decrease in the frequency but no change in the amplitude of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs).
CellLIN-10 Is a Shared Component of the Polarized Protein Localization Pathways in Neurons and Epithelia
270 Citations1998Christopher Rongo, Charles W. Whitfield +3 more
Testing the model that neurons and epithelial cells use a shared mechanism for polarized protein sorting by comparing the pathways for localizing basolateral and postsynaptic proteins in C. elegans found that these interneurons utilize at least two separate post Synaptic localization pathways.
Nature NeuroscienceAMPA receptor–PDZ interactions in facilitation of spinal sensory synapses
186 Citations1999Ping Li, Geoffrey A. Kerchner +5 more
It is demonstrated that protein interactions involving the GluR2/3 C terminus are important for serotonin-induced activation of silent synapses in the spinal cord and PKC is a necessary and sufficient trigger for this activation.
ScienceLearning Mechanisms: The Case for CaM-KII
147 Citations1997John Lisman, Robert C. Malenka +2 more
The results show that the persistent change is likely to be phosphorylation of the postsynaptic glutamate receptor known as the AMPA receptor, and how these results fit in with other findings in the literature is discussed.
Current Opinion in Cell BiologyOrganization and regulation of proteins at synapses
127 Citations1999Jee Hae Kim, Richard L. Huganir
This work has shown that the major excitatory neurotransmitter receptors in the brain, the glutamate receptors, are associated with many different molecules that are involved in the formation of elaborate synaptic cytoskeletal networks and signal transduction cascades.
Journal of NeuroscienceCyclic AMP and synaptic activity-dependent phosphorylation of AMPA- preferring glutamate receptors
126 Citations1994Craig Blackstone, Timothy H. Murphy +3 more
The results indicate that AMPA receptors containing the GluR1 subunit may be regulated by extracellular signals working through the cAMP second messenger system as well as by synaptic activity, possibly acting through protein kinase C.
NeuroscienceIntroduction of the glutamate receptor subunit 1 into motor neurons in vitro and in vivo using a recombinant herpes simplex virus
121 Citations1997Rachael L. Neve, James R. Howe +2 more
Herpes simplex virus provides a versatile tool for manipulating the glutamate receptor phenotype of postmitotic neurons and will permit study of the role of individual glutamate receptor subunits in neuronal physiology and pathophysiology.
Journal of Biological ChemistryCharacterization of the Interactions between PDZ Domains of the Protein-tyrosine Phosphatase PTPL1 and the Carboxyl-terminal Tail of Fas
48 Citations1997Jan Saras, Ulla Engström +2 more
Using a peptide binding assay, it is shown that not only PDZ 2 but also PDZ 4 of PTPL1 interacts with high affinity with peptides derived from the C terminus of Fas, a member of the tumor necrosis factor receptor family.
Journal of NeurophysiologyMechanisms of Potentiation by Calcium-Calmodulin Kinase II of Postsynaptic Sensitivity in Rat Hippocampal CA1 Neurons
47 Citations1997Aneil M. Shirke, Roberto Malinow
The hypothesis that CaMKII increases postsynaptic responsiveness by increasing the available number of active alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate channels is supported and it is suggested that a similar process may occur during the expression of long-term potentiation.
The Journal of BiochemistryEmerging Roles of Dlg-Like PDZ Proteins in the Organization of the NMDA-Type Glutamatergic Synapse
21 Citations1998T. Nagano, Hussam Jourdi +1 more
This review focuses on the best characterized PDZ-containing proteins that interact with N-methyl-D-aspartate (NMDA)-type glutamate receptors and discusses their functions in synaptic organization.
Methods in enzymology on CD-ROM/Methods in enzymology[20] Analysis of ion channel associated proteins
12 Citations1999Michael Wysznski, Morgan Sheng
This chapter considers the approaches for confirming and analyzing an interaction between an ion channel and its putative interacting protein, using as a primary example the association between PSD-95 and Shaker K + channels and N-methyl-D-aspartate (NMDA) receptors.