Pathway
Glutamate binding, activation of AMPA receptors and synaptic plasticity
Excitatory synaptic transmission in the brain is carried out by glutamate receptors through the activation of both ionotropic and metabotropic receptors. Ionotropic glutamate receptors are of three subtypes based on distinct physiologic properties and their differential binding of exogenous ligands namely NMDA (N-methyl D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and Kainate. The ionotropic receptors are glutamate gated ion channels that initiate signaling by influx of ions, and are comprised of subunits with distinct structures and distinguished based on their agonist binding. Even though all three types of receptors are found at the glutamatergic synapses yet they exhibit great diversity in the synaptic distribution. The metabotropic glutamate receptors are a family of G-protein coupled receptors that are slow acting. Fast excitatory synaptic transmission is carried out through AMPA receptors. Post-synaptic transmission involves binding of the ligand such as glutamate/AMPA to the AMPA receptor resulting in the Na influx which causes depolarization of the membrane. NMDA receptors are blocked by Mg at resting membrane potential. NMDA receptors are activated upon coincident depolarization and glutamate binding are activated following AMPA receptor activation.NMDA receptors are blocked by Mg at resting
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membrane potential. NMDA receptors are Ca permeable and their activity leads to increase in Ca which, leads to upregulation of AMPA receptors at the synapse which causes the long lasting excitatory post-synaptic potential (EPSP) which forms the basis of long term potentiation (LTP). LTP is one form of synaptic plasticity wherein the strength of the synapses is enhanced by either change in the number, increase in the efficacy by phosphorylation or change in the type of receptors. Phosphorylation of AMPA receptors changes the localization of the receptors, increases the single channel conductance, and increases the probability of open channel. GluR1 has four phosphorylation sites; serine 818 (S818) is phosphorylated by PKC and is necessary for LTP, serine 831 (S831) is phosphorylated by CaMKII that increases the delivery of receptors to the synapse and also increased their single channel conductance, threonine (T840) is implicated in LTP. Serine 845 (S845) is phosphorylated by PKA which regulates open channel probability. Long term depression is another form of plasticity wherein the number of AMPA receptors is diminished by either phosphorylation of GluR2 at Ser880 or dephosphorylation of GluR1 by protein phosphatase1, protein phosphatase 2A and protein phosphatase 2B (calcineurin).
What the reference databases state
Statements
26 statements
26 statements · 1 reference database · Subject: Glutamate binding, activation of AMPA receptors and synaptic plasticity · Sources: Reactome
- AKAP5 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- AP2A1 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- CACNG2 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- CACNG3 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- CACNG4 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- CAMK2A participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- CAMK2B participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- CAMK2D participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- CAMK2G participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- DLG1 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- DLG4 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- EPB41L1 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
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- GRIA1 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- GRIA2 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- GRIA3 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- GRIA4 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- GRIP1 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- GRIP2 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- MDM2 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- MYO6 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- NSF participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- PICK1 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- PRKCA participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- PRKCB participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- PRKCG participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only
- TSPAN7 participates in Glutamate binding, activation of AMPA receptors and synaptic plasticityProteinReactome R-HSA-399721Inferred only