Regulation of AMPA receptors and synaptic plasticity

Santos, Sandra D.; Carvalho, Ana Luı́sa; Caldeira, Margarida V.; Duarte, Carlos B.

doi:10.1016/j.neuroscience.2008.02.037

Cited by 115 publications

(101 citation statements)

References 285 publications

(349 reference statements)

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“…The role of PKC in mGluR-mediated LTD involving GluR2-containing AMPA receptors is well described in the cerebellum but to a lesser degree in cortical areas (Linden and Connor, 1993;Kim et al, 2001;Santos et al, 2009). We have shown previously that paired-burst-induced LTD involves mGluR-mediated activation of PKC and AMPAR endocytosis (Birtoli and Ulrich, 2004;Czarnecki et al, 2007).…”

Section: Discussionmentioning

confidence: 87%

Removal of Synaptic Ca²⁺-Permeable AMPA Receptors during Sleep

Lanté

Toledo-Salas²,

Ondrejčák³

et al. 2011

J. Neurosci.

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There is accumulating evidence that sleep contributes to memory formation and learning, but the underlying cellular mechanisms are incompletely understood. To investigate the impact of sleep on excitatory synaptic transmission, we obtained whole-cell patch-clamp recordings from layer V pyramidal neurons in acute slices of somatosensory cortex of juvenile rats (postnatal days 21-25). In animals after the dark period, philanthotoxin 74 (PhTx)-sensitive calcium-permeable AMPA receptors (CP-AMPARs) accounted for ϳ25% of total EPSP size, and current-voltage (I-V) relationships of the underlying EPSCs showed inward rectification. In contrast, in similar experiments after the light period, EPSPs were PhTx insensitive with linear I-V characteristics, indicating that CP-AMPARs were less abundant. Combined EEG and EMG recordings confirmed that slow-wave sleep-associated delta wave power peaked at the onset of the more quiescent, lights-on phase of the cycle. Subsequently, we show that burst firing, a characteristic action potential discharge mode of layer V pyramidal neurons during slow-wave sleep has a dual impact on synaptic AMPA receptor composition: repetitive burst firing without synaptic stimulation eliminated CP-AMPARs by activating serine/threonine phosphatases. Additionally, repetitive burst-firing paired with EPSPs led to input-specific long-term depression (LTD), affecting Ca 2ϩ impermeable AMPARs via protein kinase C signaling. In agreement with two parallel mechanisms, simple bursts were ineffective after the light period but paired bursts induced robust LTD. In contrast, incremental LTD was generated by both conditioning protocols after the dark cycle. Together, our results demonstrate qualitative changes at neocortical glutamatergic synapses that can be induced by discharge patterns characteristic of non-rapid eye movement sleep.

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Section: Discussionmentioning

confidence: 87%

Removal of Synaptic Ca²⁺-Permeable AMPA Receptors during Sleep

Lanté

Toledo-Salas²,

Ondrejčák³

et al. 2011

J. Neurosci.

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“…Common phosphorylation signaling motifs such as kinase divergence, where a single protein kinase phosphorylates multiple target sites, and kinase convergence, where a single site is phosphorylated by multiple protein kinases, are found within the C terminus of AMPAR GluA1 subunits (2,32). In addition to these intermolecular signaling motifs, our results suggest that the close proximity of Thr-840 and Ser-845 gives rise to an intramolecular phosphorylation signaling motif in GluA1 where phosphorylation of one site interferes with phosphorylation of the other.…”

Section: Discussionmentioning

confidence: 99%

“…Phosphorylation-dependent changes in the activity and trafficking of postsynaptic ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) 2 are thought to have a key role in NMDA receptor (NMDAR)-dependent forms of synaptic plasticity such as long term potentiation (LTP) and long term depression (LTD) (1,2). Functional AMPARs are formed from tetrameric combinations of different subunits (GluA1-GluA4), and previous studies have identified a number of phosphorylation sites in the cytoplasmic C-terminal tails of these subunits that may be involved in synaptic plasticity (3).…”

mentioning

confidence: 99%

Inhibitory Interactions between Phosphorylation Sites in the C Terminus of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid-type Glutamate Receptor GluA1 Subunits

Gray¹,

Guglietta²,

Khakh

et al. 2014

Journal of Biological Chemistry

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Background: AMPA receptor (AMPAR) GluA1 subunits contain multiple phosphorylation sites. Results: Distinct Ca 2ϩ -dependent signaling pathways regulate GluA1 phosphorylation at Thr-840 and Ser-845, and phosphorylation of one site inhibits phosphorylation of the other. Conclusion:Interactions between Thr-840 and Ser-845 provides a mechanism for conditional regulation of AMPARs. Significance: Our results reveal a novel mechanism for regulating AMPAR function at excitatory synapses.

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“…Phosphorylation regulates the endocytosis of AMPA receptors (15,16) and NMDA receptors (17). PKC phosphorylation has been shown to influence KAR trafficking and plasticity (5-7), but until recently the roles of specific KAR subunit phosphorylation had not been well defined.…”

Section: Discussionmentioning

confidence: 99%

Agonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis

Konopacki¹,

Jaafari²,

Rocca³

et al. 2011

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

106

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The surface expression and regulated endocytosis of kainate (KA) receptors (KARs) plays a critical role in neuronal function. PKC can modulate KAR trafficking, but the sites of action and molecular consequences have not been fully characterized. Small ubiquitinlike modifier (SUMO) modification of the KAR subunit GluK2 mediates agonist-evoked internalization, but how KAR activation leads to GluK2 SUMOylation is unclear. Here we show that KA stimulation causes rapid phosphorylation of GluK2 by PKC, and that PKC activation increases GluK2 SUMOylation both in vitro and in neurons. The intracellular C-terminal domain of GluK2 contains two predicted PKC phosphorylation sites, S846 and S868, both of which are phosphorylated in response to KA. Phosphomimetic mutagenesis of S868 increased GluK2 SUMOylation, and mutation of S868 to a nonphosphorylatable alanine prevented KA-induced SUMOylation and endocytosis in neurons. Infusion of SUMO-1 dramatically reduced KAR-mediated currents in HEK293 cells expressing WT GluK2 or nonphosphorylatable S846A mutant, but had no effect on currents mediated by the S868A mutant. These data demonstrate that agonist activation of GluK2 promotes PKCdependent phosphorylation of S846 and S868, but that only S868 phosphorylation is required to enhance GluK2 SUMOylation and promote endocytosis. Thus, direct phosphorylation by PKC and GluK2 SUMOylation are intimately linked in regulating the surface expression and function of GluK2-containing KARs.

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Regulation of AMPA receptors and synaptic plasticity

Cited by 115 publications

References 285 publications

Removal of Synaptic Ca²⁺-Permeable AMPA Receptors during Sleep

Removal of Synaptic Ca²⁺-Permeable AMPA Receptors during Sleep

Inhibitory Interactions between Phosphorylation Sites in the C Terminus of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid-type Glutamate Receptor GluA1 Subunits

Agonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis

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Regulation of AMPA receptors and synaptic plasticity

Cited by 115 publications

References 285 publications

Removal of Synaptic Ca2+-Permeable AMPA Receptors during Sleep

Removal of Synaptic Ca2+-Permeable AMPA Receptors during Sleep

Inhibitory Interactions between Phosphorylation Sites in the C Terminus of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid-type Glutamate Receptor GluA1 Subunits

Agonist-induced PKC phosphorylation regulates GluK2 SUMOylation and kainate receptor endocytosis

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Removal of Synaptic Ca²⁺-Permeable AMPA Receptors during Sleep

Removal of Synaptic Ca²⁺-Permeable AMPA Receptors during Sleep