Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors

Soto, David; Coombs, Ian D.; Kelly, Leah; Farrant, M; Cull-Candy, SG

doi:10.1038/nn1966

Cited by 167 publications

(253 citation statements)

References 51 publications

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“…TARPs also modulate the single channel conductance of AMPARs (7,16). In agreement with previous findings for GluA1 coexpressed with γ-2 (16), nonstationary fluctuation analysis revealed that fusion of GluA1 to γ-8 caused a doubling of AMPAR single channel conductance ( Fig.…”

Section: Resultssupporting

confidence: 91%

Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating

Shi¹,

Suh

Milstein

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

106

159

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Glutamate receptors of the AMPA subtype (AMPARs) mediate fast synaptic transmission in the brain. These ionotropic receptors rely on auxiliary subunits known as transmembrane AMPAR regulatory proteins (TARPs) for both trafficking and gating. Recently, a second family of AMPAR binding proteins, referred to as cornichons, were identified and also proposed to function as auxiliary subunits. Cornichons are transmembrane proteins that modulate AMPAR function in expression systems much like TARPs. In the present study we compare the role of cornichons in controlling AMPA receptor function in neurons and HEK cells to that of TARPs. Cornichons mimic some, but not all, of the actions of TARPs in HEK cells; their role in neurons, however, is more limited. Although expressed cornichons can affect the trafficking of AMPARs, they were not detected on the surface of neurons and failed to alter the kinetics of endogenous AMPARs. This neuronal role is more consistent with that of an endoplasmic reticulum (ER) chaperone rather than a bona fide auxiliary subunit.stargazin | synapse | auxiliary subunit | hippocampus

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Section: Resultssupporting

confidence: 91%

Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating

Shi¹,

Suh

Milstein

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

106

159

View full text Add to dashboard Cite

show abstract

“…Thus, in addition to their well-characterised role in determining the biophysical properties of AMPARs, TARPs also play a key role in synaptic AMPAR retention under basal and activity-dependent conditions. Beyond the synaptic trapping of AMPARs, the TARPs Stargazin and γ5 directly reduce the polyamine sensitivity of CP-AMPARs 121,122 . Because polyamine block is a parameter used to determine the GluA2 content of the receptors, the presence or absence of TARPs can therefore complicate unambiguous determination of subunit content and necessitates careful consideration of the role of TARPs in the trafficking of CP-versus CI-AMPARs.…”

Section: Ampar Auxiliary Subunitsmentioning

confidence: 99%

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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“…Moreover, GluA2 receptor mutants (N619C and N619K) have much decreased calcium permeability, but their rectification properties are similar to wild-type receptors, suggesting that their spermine sensitivity is the same (Jatzke et al, 2003). In a more physiological situation, addition of stargazin to AMPA receptors decreases their sensitivity to spermine without changing their calcium permeability (Soto et al, 2007). Therefore, these two channel properties are related but rely on different mechanisms.…”

Section: Properties Of the Gluk3 Channel Porementioning

confidence: 99%

Atypical Functional Properties of GluK3-Containing Kainate Receptors

Perrais¹,

Coussen²,

Mulle³

2009

J. Neurosci.

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The properties of synaptic receptors determine their mode of action at presynaptic and postsynaptic loci. Here, we investigated the atypical biophysical properties of GluK3-containing kainate receptors, which contribute to presynaptic facilitation at hippocampal mossy fiber synapses. We show, using fast glutamate applications on outside-out patches and kinetic modeling, that the low sensitivity of GluK3 receptors for glutamate is attributable to fast desensitization of partially bound receptors. Consequently, these receptors can only be activated by fast transients of high glutamate concentration. In addition, GluK3 receptors are very sensitive to voltage-dependent block by intracellular spermine that precludes activation of substantial currents at potentials positive to Ϫ50 mV. Two specific residues within the channel pore define this high-affinity site. Finally, GluK3 are calcium permeable in the same way as unedited GluK2 receptors. These receptors present unique properties among AMPA/kainate receptors that could reflect a specialized presynaptic function.

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Stargazin attenuates intracellular polyamine block of calcium-permeable AMPA receptors

Cited by 167 publications

References 51 publications

Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating

Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating

Synaptic AMPA receptor composition in development, plasticity and disease

Atypical Functional Properties of GluK3-Containing Kainate Receptors

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