Control of GluR1 AMPA Receptor Function by cAMP-Dependent Protein Kinase

By T. Banke, D. Bowie, Hey-Kyoung Lee, Richard L. Huganir, A. Schousboe, S. Traynelis. Journal of Neuroscience, 2000

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Modulation of postsynaptic AMPA receptors in the brain by phosphorylation may play a role in the expression of synaptic plasticity at central excitatory synapses. It is known from biochemical studies that GluR1 AMPA receptor subunits can be phosphorylated within their C terminal by cAMP-dependent protein kinase A (PKA), which is colocalized with the phosphatase calcineurin (i.e., phosphatase 2B). We have examined the effect of PKA and calcineurin on the time course, peak open probability (PO,PEAK), and single-channel properties of glutamateevoked responses for neuronal AMPA receptors and homomeric GluR1(flip) receptors recorded in outside-out patches. Inclusion of purified catalytic subunit Cα-PKA in the pipette solution increased neuronal AMPA receptorPO,PEAK (0.92) compared with recordings made with calcineurin included in the pipette (PO,PEAK 0.39). Similarly, Cα-PKA increased PO,PEAK for recombinant GluR1 receptors (0.78) compared with patches excised from cells cotransfected with a cDNA encoding the PKA peptide inhibitor PKI (PO,PEAK 0.50) or patches with calcineurin included in the pipette (PO,PEAK 0.42). Neither PKA nor calcineurin altered the amplitude of single-channel subconductance levels, weighted mean unitary current, mean channel open period, burst length, or macroscopic response waveform for recombinant GluR1 receptors. Substitution of an amino acid at the PKA phosphorylation site (S845A) on GluR1 eliminated the PKA-induced increase in PO,PEAK, whereas the mutation of a Ca2+,calmodulin-dependent kinase II and PKC phosphorylation site (S831A) was without effect. These results suggest that AMPA receptor peak response open probability can be increased by PKA through phosphorylation of GluR1 Ser845.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b5492ef1b107c54fc82d86c5d9b5e8420d4e992a

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Citations in the corpus

Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression. (2003, background): “The GluR1 subunit of the AMPA receptor is one likely candidate substrate (Banke et al., 2000; Lee al., 2002; Chain et al., 1999; DiAntonio et al., 2001; Ehlers, 2003; Hegde et al., 1997; Jiang et al., 1998; Speese etet al., 2000a; Tavalin et al., 2002).”
Impact of aging on hippocampal function: plasticity, network dynamics, and cognition. (2003, background): “Phosphorylation of serine 845 may cause an increase in the opening probability of the AMPA receptor (Banke et al., 2000), while phosphorylation of serine 831 may cause an increase in the single-channel conductance of the AMPA receptor (Derkach et al.”
Glutamate Receptor Ion Channels: Structure, Regulation, and Function (2010, background): “, 1996) increases the open probability of homomeric GluA1 channels studied in outside-out patches (Banke et al., 2000), which has been proposed to reflect a change in the equilibrium of GluA1 with an inactive state, perhaps relating to phosphodependent binding of intracellular regulatory proteins.”
Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity (2009, neutral): “On noxious stimulation, PKA phosphorylates GluR1 subunits,(87,88,214) leading to an insertion of these receptors into the synapse(84,93) and thereby an increase in synaptic strength.(20) Phosphorylation of GluR1-containing AMPAR by PKC and CaMKII also increases the excitability of nociceptive neuron”
Handbook of ion channels (2015, background): “Although control of gating of homomeric receptors in expression systems is appreciable (Banke et al., 2000; Derkach et al., 1999; Kristensen et al., 2011), acute reversal is not reported and unsurprisingly, the effects on native heteromers are less pronounced.”
Assembly of a β2‐adrenergic receptor—GluR1 signalling complex for localized cAMP signalling (2010, background): “S845 phosphorylation might also enhance the activity of GluR1-containing AMPARs by increasing their open prob- ability (Banke et al, 2000), which could have contributed to the increase in AMPAR responses we observed in acute hippocampal and PFC slices.”
Regulatory mechanisms of AMPA receptors in synaptic plasticity (2007, background): “Phosphorylation of AMPARs results in modulation of receptor propertie”
Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity (2000, background): “Phosphorylation of either of these sites potentiates AMPA receptor function through distinct biophysical mechanism”
Mechanisms of CaMKII action in long-term potentiation (2012, background): “73 ); S845, which is phosphorylated by protein kinase A (PKA”
Neurobiology of Relapse to Heroin and Cocaine Seeking: A Review (2002, background): “Cornish and Kalivas (1999) found that activation of AMPA receptors in the NAc reinstate cocaine seeking, and PKA modulates AMPA receptor activity (Banke et al., 2000).”
The cell biology of synaptic plasticity: AMPA receptor trafficking. (2007, background): “…is another critical event in LTP. Intracellular perfusion of PKA into GluR1-transfected HEK 293 cells resulted in a 40% potentiation of the peak amplitude of the whole-cell glutamate-gated current (Roche et al. 1996) and regulated the openchannel probability of the receptor (Banke et al. 2000).”
Synaptic Plasticity: Multiple Forms, Functions, and Mechanisms (2008, background): “This dephosphorylation event may contribute to the expression of LTD, as it decreases the AMPAR openchannel probability (Banke et al, 2000), and mice with knock-in alanine substitution of both Ser845 and Ser831 (a CaMKII-substrate site) exhibit impaired NMDAR-dependent LTD (Lee et al, 2003).”
AKAP signalling complexes: focal points in space and time (2004, background): “This Ser residue is an important site for the regulation of AMPA-receptor function during the induction of long-term synaptic depression, which is a molecular model for hippocampal learning and memory acquisitio”