General Information:

Id: 4,719
Diseases: Neurological
Mammalia
review
Reference: Mao LM et al.(2011) Post-translational modification biology of glutamate receptors and drug addiction Front Neuroanat 5: 19 [PMID: 21441996]

Interaction Information:

Comment Group I metabotropic glutamate receptors (mGluR1/5 subtypes) are positively coupled to phospholipase Cbeta1 through Galphaq proteins (GNAQ).
Formal Description
Interaction-ID: 46758

gene/protein

GRM1

interacts (colocalizes) with

gene/protein

PLCB1

through Galphaq proteins;
Drugbank entries Show/Hide entries for GRM1
Comment The GluA1 C-terminus has four identified phosphorylation sites at serine 818 (S818), S831, threonine 840 (T840), and S845. Acute phosphorylation of GluA1 S818 by PKC promoted GluA1 synaptic incorporation and an activity-dependent form of synaptic plasticity, long-term potentiation.
Formal Description
Interaction-ID: 46763

gene/protein

Protein kinase C

increases_phosphorylation of

gene/protein

GRIA1

at position Ser818 and Ser831;
Drugbank entries Show/Hide entries for GRIA1
Comment Group I metabotropic glutamate receptors (mGluR1/5 subtypes) are positively coupled to phospholipase Cbeta1 through Galphaq proteins (GNAQ).
Formal Description
Interaction-ID: 46772

gene/protein

GNAQ

increases_activity of

gene/protein

PLCB1

through Galphaq proteins;
Comment Acute phosphorylation of GluA1 Ser818 by PKC promoted GluA1 synaptic incorporation and an activity-dependent form of synaptic plasticity, long-term potentiation. PKC/CaMKII- (Ca2+/calmodulin-dependent protein kinase II) -sensitive GluA1-Ser831 and PKA-sensitive Ser845 phosphorylation potentiated AMPAR currents and augmented also LTP. GluA1-Ser845/Ser831 phosphorylation is likely to be upregulated to increase surface AMPAR expression and thereby enhance AMPAR transmission related to behavioral plasticity.
Formal Description
Interaction-ID: 46773

protein modification

GRIA1-phos

increases_activity of

process

long-term synaptic potentiation

at position Ser818, Ser831, and Ser845;
Comment Acute phosphorylation of GluA1 S818 by PKC promoted GluA1 synaptic incorporation and an activity-dependent form of synaptic plasticity, long-term potentiation.
Formal Description
Interaction-ID: 46774

protein modification

GRIA1-phosSer818

affects_activity of

process

regulation of synaptic plasticity

Comment The GluA1 C-terminus has four identified phosphorylation sites at serine 818 (S818), S831, threonine 840 (T840), and S845. PKC/CaMKII- (Ca2+/calmodulin-dependent protein kinase II) -sensitive S831 and PKA-sensitive S845 phosphorylation potentiated AMPAR currents and augmented LTP.
Formal Description
Interaction-ID: 46776

gene/protein

CAMK2

increases_phosphorylation of

gene/protein

GRIA1

at position Ser831 potentiated AMPAR currents and augmented LTP;
Drugbank entries Show/Hide entries for GRIA1
Comment The GluA1 C-terminus has four identified phosphorylation sites at serine 818 (S818), S831, threonine 840 (T840), and S845. PKC/CaMKII- (Ca2+/calmodulin-dependent protein kinase II) -sensitive S831 and PKA-sensitive S845 phosphorylation potentiated AMPAR currents and augmented LTP. GluA1-Ser845/Ser831 phosphorylation is likely to be upregulated to increase surface AMPAR expression and thereby enhance AMPAR transmission related to behavioral plasticity.
Formal Description
Interaction-ID: 46781

complex/PPI

Protein kinase A

increases_phosphorylation of

gene/protein

GRIA1

at position Ser845 potentiated AMPAR currents and augmented LTP;
Drugbank entries Show/Hide entries for GRIA1
Comment The GluA1 C-terminus has four identified phosphorylation sites at serine 818 (S818), S831, threonine 840 (T840), and S845. T840 is dephosphorylated by NMDAR signals, which is implicated in long-term depression.
Formal Description
Interaction-ID: 46795

protein modification

GRIA1-phosThr840

affects_activity of

process

long-term synaptic depression

Comment GRIA1 is part of the AMPA receptor complex.
Formal Description
Interaction-ID: 46796

gene/protein

GRIA1

is_part_of

complex/PPI

AMPA receptor complex

Drugbank entries Show/Hide entries for GRIA1
Comment Dopamine is a strong regulator of the site-specific phosphorylation of striatal GluA1 subunits. By stimulating D1 dopamine receptors and associated cAMP/ PKA pathways, the D1 agonist and psychostimulants (cocaine and amphetamine) increased GluA1 phosphorylation preferentially at Ser845 in striatal neurons.
Formal Description
Interaction-ID: 46806

drug/chemical compound

Dopamine

increases_phosphorylation of

gene/protein

GRIA1

in striatal neurons; preferentially at Ser845
Drugbank entries Show/Hide entries for Dopamine or GRIA1
Comment Dopamine is a strong regulator of the site-specific phosphorylation of striatal GluA1 subunits. By stimulating D1 dopamine receptors and associated cAMP/ PKA pathways, the D1 agonist and psychostimulants (cocaine and amphetamine) increased GluA1 phosphorylation preferentially at Ser845 in striatal neurons.
Formal Description
Interaction-ID: 46816

drug/chemical compound

Amfetamine

increases_phosphorylation of

gene/protein

GRIA1

in striatal neurons; preferentially at Ser845
Drugbank entries Show/Hide entries for GRIA1
Comment The dopamine D2 receptor inhibits GluA1- Ser845 phosphorylation.
Formal Description
Interaction-ID: 46873

gene/protein

DRD2

decreases_phosphorylation of

gene/protein

GRIA1

at Ser845
Drugbank entries Show/Hide entries for DRD2 or GRIA1
Comment Cocaine-sensitized or heroin self-administering rodents were associated with increased phosphorylation at GluA1-Ser845 in the NAc (nucleus accumbens) and at Ser831 in the CPu (caudate-putamen). Increased accumbens shell GluA1-Ser831 phosphorylation was seen in animals showing reinstatement of cocaine-seeking.
Formal Description
Interaction-ID: 46874

drug/chemical compound

Cocaine

increases_phosphorylation of

gene/protein

GRIA1

at Ser845 in the NAc (nucleus accumbens) and at Ser831 in the CPu (caudate-putamen) in cocaine-sensitized rodents
Drugbank entries Show/Hide entries for Cocaine or GRIA1
Comment In addition to GluA1, elevated GluA2-Ser880 phosphorylation in the NAc was related to reinstatement of cocaine-seeking.
Formal Description
Interaction-ID: 46876

drug/chemical compound

Cocaine

increases_phosphorylation of

gene/protein

GRIA2

at Ser880
Drugbank entries Show/Hide entries for Cocaine or GRIA2
Comment Cocaine-sensitized or heroin self-administering rodents were associated with increased phosphorylation at GluA1-Ser845 in the NAc (nucleus accumbens) and at Ser831 in the CPu (caudate-putamen).
Formal Description
Interaction-ID: 46934

drug/chemical compound

Diamorphine

increases_phosphorylation of

gene/protein

GRIA1

at Ser845 in the NAc (nucleus accumbens) and at Ser831 in the CPu (caudate-putamen) in heroin self-administering rodents
Drugbank entries Show/Hide entries for GRIA1
Comment GRIA1-T840 is not a substrate of the common kinases such as PKA, PKC, or CaMKII, but it appears to be a substrate of p70S6 kinase. T840 is dephosphorylated by NMDAR signals, which is implicated in long-term depression.
Formal Description
Interaction-ID: 46982

gene/protein

RPS6KB1

increases_phosphorylation of

gene/protein

GRIA1

at Thr840;
Drugbank entries Show/Hide entries for GRIA1
Comment Group I metabotropic glutamate receptors (mGluR1/5 subtypes) are positively coupled to phospholipase Cbeta1 through Galphaq proteins (GNAQ).
Formal Description
Interaction-ID: 49373

gene/protein

GRM5

interacts (colocalizes) with

gene/protein

PLCB1

through Galphaq proteins;
Drugbank entries Show/Hide entries for GRM5