Subunit-specific role for the amino-terminal domain of AMPA receptors in synaptic targeting.
Javier Díaz-Alonso,Yujiao J. Sun,Adam J. Granger,Jonathan M. Levy,Sabine M. Blankenship,Roger A. Nicoll +5 more
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TLDR
A role for the ATD is uncovered in subunit-specific synaptic trafficking of AMPARs, both constitutively and during plasticity, as well as how LTP, induced postsynaptically, engages these extracellular trafficking motifs and what specific cleft proteins participate in the process remain to be elucidated.Abstract:
The amino-terminal domain (ATD) of AMPA receptors (AMPARs) accounts for approximately 50% of the protein, yet its functional role, if any, remains a mystery. We have discovered that the translocation of surface GluA1, but not GluA2, AMPAR subunits to the synapse requires the ATD. GluA1A2 heteromers in which the ATD of GluA1 is absent fail to translocate, establishing a critical role of the ATD of GluA1. Inserting GFP into the ATD interferes with the constitutive synaptic trafficking of GluA1, but not GluA2, mimicking the deletion of the ATD. Remarkably, long-term potentiation (LTP) can override the masking effect of the GFP tag. GluA1, but not GluA2, lacking the ATD fails to show LTP. These findings uncover a role for the ATD in subunit-specific synaptic trafficking of AMPARs, both constitutively and during plasticity. How LTP, induced postsynaptically, engages these extracellular trafficking motifs and what specific cleft proteins participate in the process remain to be elucidated.read more
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The AMPA Receptor Code of Synaptic Plasticity.
TL;DR: The AMPAR code suggests that AMPAR variants will be predictive of the types and extent of synaptic plasticity that can occur and that a hierarchy exists such that certain AMPARs will be disproportionally recruited to synapses during LTP/homeostatic scaling up, or removed during LTD/homeOSTatic scaling down.
Journal ArticleDOI
Transcellular Nanoalignment of Synaptic Function.
TL;DR: The organization of each compartment is described and it is proposed that this architecture may allow for precise synaptic information exchange and may be modulated to contribute to the remarkable plasticity of brain function.
Journal ArticleDOI
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.
Kasper B. Hansen,Lonnie P. Wollmuth,Derek Bowie,Hiro Furukawa,Frank S. Menniti,Alexander I. Sobolevsky,Geoffrey T. Swanson,Sharon A. Swanger,Ingo H. Greger,Terunaga Nakagawa,Chris J. McBain,Vasanthi Jayaraman,Chian-Ming Low,Mark L. Dell’Acqua,Jeffrey S. Diamond,Chad R. Camp,Riley E. Perszyk,Hongjie Yuan,Stephen F. Traynelis +18 more
TL;DR: In this paper, the authors review insights from more than 3 decades of iGluR studies with an emphasis on the progress that has occurred in the past decade, covering structure, function, pharmacology, roles in neurophysiology, and therapeutic implications for all classes of receptors assembled from the subunits encoded by the 18 ionotropic glutamate receptor genes.
Journal ArticleDOI
Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM.
TL;DR: The structures of 10 distinct native AMPA receptor complexes by single-particle cryo–electron microscopy (cryo-EM) are elucidated, finding that receptor subunits are arranged nonstochastically, with the GluA2 subunit preferentially occupying the B and D positions of the tetramer and with triheteromeric assemblies comprising a major population ofnative AMPA receptors.
Journal ArticleDOI
Functional organization of postsynaptic glutamate receptors.
TL;DR: This review will focus on the mechanisms that control the organization of glutamate receptors at the postsynaptic membrane with respect to the release site, and discuss how this organization could regulate synapse physiology.
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AMPA Receptor Trafficking and Synaptic Plasticity
TL;DR: The growing literature that supports a critical role for AMPA receptors trafficking in LTP and LTD is reviewed, focusing on the roles proposed for specific AMPA receptor subunits and their interacting proteins.
Journal ArticleDOI
Driving AMPA Receptors into Synapses by LTP and CaMKII: Requirement for GluR1 and PDZ Domain Interaction
Yasunori Hayashi,Song-Hai Shi,José A. Esteban,Antonella Piccini,Jean Christophe Poncer,Roberto Malinow +5 more
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.
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Rapid Spine Delivery and Redistribution of AMPA Receptors After Synaptic NMDA Receptor Activation
Song-Hai Shi,Yasunori Hayashi,Ronald S. Petralia,Shahid Zaman,Robert J. Wenthold,Karel Svoboda,Roberto Malinow +6 more
TL;DR: 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.
Journal ArticleDOI
Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS
Bernd Sommer,Kari Keinänen,Todd A. Verdoorn,William Wisden,Nail Burnashev,Anne Herb,Martin Köhler,Tamaki Takagi,Bert Sakmann,Peter H. Seeburg +9 more
TL;DR: These results identify a switch in the molecular and functional properties of glutamate receptors operated by alternative splicing.