Glutamate Receptor Trafficking: Endoplasmic Reticulum Quality Control Involves Ligand Binding and Receptor Function

Mah, Stephanie J.; Cornell, Elizabeth; Mitchell, Nicholas A.; Fleck, Mark W.

doi:10.1523/jneurosci.4573-04.2005

Cited by 83 publications

(98 citation statements)

References 73 publications

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“…Additional stability may be provided by stargazin (and other TARPs) as part of the native complex. Considering the close structural similarity and related findings with other iGluR (Grunwald and Kaplan, 2003;Mah et al, 2005;Valluru et al, 2005), the requirement for agonist binding may be a general property of iGluR maturation.…”

Section: Discussionmentioning

confidence: 66%

“…Point mutations in the agonist-binding domain of Caenorhabditis elegans GLR-1 (Grunwald and Kaplan, 2003), mammalian kainate (Mah et al, 2005;Valluru et al, 2005;Fleck, 2006;Priel et al, 2006), and AMPA receptor subunits (Greger et al, 2006) have been reported to impede the expression of the cognate receptors on cell surface. The nature of the responsible mechanism(s) and the importance of agonist-binding activity itself, for the transport of AMPA receptors, are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Agonist Occupancy Is Essential for Forward Trafficking of AMPA Receptors

Coleman¹,

Möykkynen²,

Jouppila³

et al. 2009

J. Neurosci.

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Agonist Occupancy Is Essential for Forward Trafficking of AMPA Receptors

Coleman¹,

Möykkynen²,

Jouppila³

et al. 2009

J. Neurosci.

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“…2, B and C, 5). Interestingly, binding site mutations in the kainate receptor GluK2 that abolish its function actually increased the tetramer fraction (50). We therefore tested the tetrameric stability of the receptor using the SDS approach either with or without glutamate in the solubilization buffer (data not shown), but did not observe any difference, possibly due to limited sensitivity of the assay.…”

Section: Discussionmentioning

confidence: 99%

The Transmembrane Domain Mediates Tetramerization of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors

Gan¹,

Dai

Zhou

et al. 2016

Journal of Biological Chemistry

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AMPA receptors (AMPARs) mediate fast excitatory neurotransmission in the central nervous system. Functional AMPARs are tetrameric complexes with a highly modular structure, consisting of four evolutionarily distinct structural domains: an amino-terminal domain (ATD), a ligand-binding domain (LBD), a channel-forming transmembrane domain (TMD), and a carboxyl-terminal domain (CTD). Here we show that the isolated TMD of the GluA1 AMPAR is fully capable of tetramerization. Additionally, removal of the extracellular domains from the receptor did not affect membrane topology or surface delivery. Furthermore, whereas the ATD and CTD contribute positively to tetramerization, the LBD presents a barrier to the process by reducing the stability of the receptor complex. These experiments pinpoint the TMD as the "tetramerization domain" for AMPARs, with other domains playing modulatory roles. They also raise intriguing questions about the evolution of iGluRs as well as the mechanisms regulating the biogenesis of AMPAR complexes.

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“…AMPARs containing both GluA1 and GluA2 follow GluA1 trafficking rules and override the ER retention of GluA2. Thus, GluA1/2 heteromers rapidly traffic from the ER to the surface whereas AMPARs without GluA1 or GluA4 transit much more slowly 77,78 (Fig. 3).…”

Section: Rna Editing Ampar Assembly and Er Exitmentioning

confidence: 98%

Synaptic AMPA receptor composition in development, plasticity and disease

2016

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. PrefaceAMPARs are assemblies of four core subunits, GluA1-4, that mediate most fast excitatory neurotransmission. The component subunits determine the functional properties of AMPARs and the prevailing view is that the subunit composition also determines AMPAR trafficking, which is dynamically regulated during development, synaptic plasticity, and in response to neuronal stress in disease. Recently, the subunit-dependence of AMPAR trafficking has been questioned leading to a reappraisal of the field. Here we review what is known, uncertain, conjectured and unknown about the roles of individual subunits and how they impact on AMPAR assembly, trafficking and function under normal and pathological conditions. IntroductionAMPA receptors (AMPARs) are a subtype of ionotropic glutamate receptors that are the 'work-horses' of fast excitatory neurotransmission in the CNS. Developmentallyand activity-regulated changes in the numbers and properties of AMPARs localized at the postsynaptic membrane are essential for excitatory synapse formation, stabilization, synaptic plasticity and neural circuit formation. Consequently, the logistics of the delivery, retention and removal of individual AMPARs with defined subunit compositions at specific synapses is highly complex. A typical cortical or hippocampal pyramidal neuron contains on the order of 10,000 synapses and the AMPARs at each synapse are independently and dynamically regulated in response to developmental cues, synaptic activity and environmental stresses. Furthermore, defects in the processes that control AMPAR assembly, trafficking and synaptic expression are intimately linked to psychiatric and neurological conditions, and also with cognitive decline in neurodegenerative diseases. Remarkable progress has been achieved in understanding how AMPAR trafficking, is orchestrated by a large array of AMPAR interacting proteins. These studies have established a set of hierarchical subunit-specific rules that control AMPAR trafficking under basal and activity-dependent conditions. Furthermore, there has been a growing appreciation that subunit composition can tune the properties of AMPARs to specific conditions. Nonetheless, how AMPARs comprising different subunits are differentially trafficked to control synaptic development, stabilisation and plasticity is a key unanswered question. Here, we provide an overview of the current state of knowledge of subunit-specific AMPAR trafficking and outline what we believe to be the key unresolved questions in the field. 2 Subunit-specific traffickingMost AMPARs are heterotetrameric assemblies of combinations of the subunits GluA1, GluA2, GluA3 and GluA4. AMPARs are expressed in both neurons and glia throughout the CNS 1 and have a turnover time of between 10 hours and 2 days depending on the type of neuron and developmental stage 2,3 . Each subunit has an identical membrane topology and c...

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Glutamate Receptor Trafficking: Endoplasmic Reticulum Quality Control Involves Ligand Binding and Receptor Function

Cited by 83 publications

References 73 publications

Agonist Occupancy Is Essential for Forward Trafficking of AMPA Receptors

Agonist Occupancy Is Essential for Forward Trafficking of AMPA Receptors

The Transmembrane Domain Mediates Tetramerization of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors

Synaptic AMPA receptor composition in development, plasticity and disease

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