Activation of kainate receptors upon glutamate binding (Homo sapiens)

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51412, 316cytosolPLCB2 GNG7 Kainate ReceptorsNa+Edited GRIK2 (GluR6) GNB3 Kainatereceptor-glutamate-Gprotein complexGNG4 Cl- GRIK5 NCALD GNGT1 GNGT2 GNG5 GNG12 Ca2+GRIK1 L-Glu GRIK1 GRIK 3 homomerNCALD GRIK2 CALM1 GNG3 Cl- GRIK5 GNG8 GNG5 GNG10 GNG4 PLCB1 Edited GRIK2 (GluR6) PLCB2 Cl- GNB4 Na+GRIK3 GNG13 Edited GRIK 1 (GluR5) L-Glu DLG3 Edited KainatereceptorsDLG3 Cl- PLCB1 GRIK4 GNB2 DLG4 PLCB3 GNG10 GRIK3 GNG7 GNB1 L-Glu GNB4 GNG2 GNG8 GRIK3 GNG12 GNGT2 CALM1 Cl- Edited GRIK 1 (GluR5) G-proteinbeta-gamma:PLC beta1/2/3GRIK3 GNB1 DLG1 GRIK3 GNGT1 L-Glu Ca2+GNG2 GRIK4 GNB3 DLG4 GRIK2 GNB5 GNG13 GNB2 DLG1 L-GluGNB5 GNG11 GNG11 Edited KainateReceptor-glutamatecomplexCl- GNG3 PLCB3 Kainatereceptor-glutamatecomplexCl- GRIK3 homomerglutamate complex


Description

Kainate receptors are found both in the presynaptc terminals and the postsynaptic neurons.
Kainate receptor activation could lead to either ionotropic activity (influx of Ca2+ or Na+ and K+) in the postsynaptic neuron or coupling of the receptor with G proteins in the presynaptic and the postsynaptic neurons.
Kainate receptors are tetramers made from subunits GRIK1-5 or GluR5-7 and KA1-2. Activation of kainate receptors made from GRIK1 or KA2 release Ca2+ from the intracellular stores in a G protein-dependent manner. The G protein involved in this process is sensitive to pertussis toxin. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 451326
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: Mahajan, SS

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Bibliography

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  1. Perrais D, Coussen F, Mulle C.; ''Atypical functional properties of GluK3-containing kainate receptors.''; PubMed Europe PMC Scholia
  2. Wilding TJ, Zhou Y, Huettner JE.; ''Q/R site editing controls kainate receptor inhibition by membrane fatty acids.''; PubMed Europe PMC Scholia
  3. Carver JM, Mansson PE, Cortes-Burgos L, Shu J, Zhou LM, Howe JR, Giordano T.; ''Cytotoxic effects of kainate ligands on HEK cell lines expressing recombinant kainate receptors.''; PubMed Europe PMC Scholia
  4. Bardoul M, Levallois C, König N.; ''Functional AMPA/kainate receptors in human embryonic and foetal central nervous system.''; PubMed Europe PMC Scholia
  5. Jane DE, Lodge D, Collingridge GL.; ''Kainate receptors: pharmacology, function and therapeutic potential.''; PubMed Europe PMC Scholia
  6. Gill MB, Vivithanaporn P, Swanson GT.; ''Glutamate binding and conformational flexibility of ligand-binding domains are critical early determinants of efficient kainate receptor biogenesis.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114901view16:41, 25 January 2021ReactomeTeamReactome version 75
113061view10:59, 2 November 2020ReactomeTeamReactome version 74
112295view15:12, 9 October 2020ReactomeTeamReactome version 73
102017view15:16, 26 November 2018Marvin M2Ontology Term : 'neuron-to-neuron signaling pathway via the chemical synapse' added !
101670view13:49, 1 November 2018DeSlOntology Term : 'signaling pathway' added !
101669view13:49, 1 November 2018DeSlOntology Term : 'neuron' added !
101657view11:51, 1 November 2018ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
CALM1 ProteinP0DP23 (Uniprot-TrEMBL)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Cl- MetaboliteCHEBI:17996 (ChEBI)
DLG1 ProteinQ12959 (Uniprot-TrEMBL)
DLG3 ProteinQ92796 (Uniprot-TrEMBL)
DLG4 ProteinP78352 (Uniprot-TrEMBL)
Edited GRIK 1 (GluR5) ProteinP39086 (Uniprot-TrEMBL) Glutamine at position 636 is replaced by arginine in an editing step which occurs posttranscriptionally.
Edited GRIK2 (GluR6) ProteinQ13002 (Uniprot-TrEMBL) GRIK2 is edited at the Q/R site at 621 where the glutamine is edited to arginine. GRIK2 is also edited at 571 (Y/C) where a tyrosine residue is changed to cysteine and 567 (I/V) where an isoleucine is changed to valine. All three sites are edited postranscriptionally. A fully edited GRIK2 at all three sites is totally impermeable to calcium ions.
Edited Kainate

Receptor-glutamate

complex
ComplexR-HSA-451304 (Reactome)
Edited Kainate receptorsComplexR-HSA-451279 (Reactome) Kainate receptors are formed by the assembly of four subunits. GluR5-7 (GRIK, glutamate receptor, ionotropic Kainate 1-3) form functional homomers whereas, KA1 and KA2 or GRIK4,5 form functional heteromers with GRIK1/2/3. Kainate receptor subunits bind Cl- ion in the anion binding site in the ligand binding domain. The dimer is stabilized by the presence of one Cl- ion which binds within the dimer interface.
G-protein

beta-gamma:PLC beta

1/2/3
ComplexR-HSA-398037 (Reactome)
GNB1 ProteinP62873 (Uniprot-TrEMBL)
GNB2 ProteinP62879 (Uniprot-TrEMBL)
GNB3 ProteinP16520 (Uniprot-TrEMBL)
GNB4 ProteinQ9HAV0 (Uniprot-TrEMBL)
GNB5 ProteinO14775 (Uniprot-TrEMBL)
GNG10 ProteinP50151 (Uniprot-TrEMBL)
GNG11 ProteinP61952 (Uniprot-TrEMBL)
GNG12 ProteinQ9UBI6 (Uniprot-TrEMBL)
GNG13 ProteinQ9P2W3 (Uniprot-TrEMBL)
GNG2 ProteinP59768 (Uniprot-TrEMBL)
GNG3 ProteinP63215 (Uniprot-TrEMBL)
GNG4 ProteinP50150 (Uniprot-TrEMBL)
GNG5 ProteinP63218 (Uniprot-TrEMBL)
GNG7 ProteinO60262 (Uniprot-TrEMBL)
GNG8 ProteinQ9UK08 (Uniprot-TrEMBL)
GNGT1 ProteinP63211 (Uniprot-TrEMBL)
GNGT2 ProteinO14610 (Uniprot-TrEMBL)
GRIK 3 homomerComplexR-HSA-450196 (Reactome)
GRIK1 ProteinP39086 (Uniprot-TrEMBL)
GRIK2 ProteinQ13002 (Uniprot-TrEMBL)
GRIK3 ProteinQ13003 (Uniprot-TrEMBL)
GRIK3 homomer glutamate complexComplexR-HSA-500705 (Reactome)
GRIK4 ProteinQ16099 (Uniprot-TrEMBL)
GRIK5 ProteinQ16478 (Uniprot-TrEMBL)
Kainate

receptor-glutamate

complex
ComplexR-HSA-451281 (Reactome)
Kainate receptor-glutamate-Gprotein complexComplexR-HSA-500703 (Reactome)
Kainate ReceptorsComplexR-HSA-450885 (Reactome) Kainate receptors are formed by the assembly of four subunits. GluR5-7 (GRIK, glutamate receptor, ionotropic Kainate 1-3) form functional homomers whereas, KA1 and KA2 or GRIK4,5 form functional heteromers with GRIK1/2/3. Kainate receptor subunits bind Cl- ion in the anion binding site in the ligand binding domain. The dimer is stabilized by the presence of one Cl- ion which binds within the dimer interface.
L-Glu MetaboliteCHEBI:29985 (ChEBI)
L-GluMetaboliteCHEBI:29985 (ChEBI)
NCALD ProteinP61601 (Uniprot-TrEMBL)
Na+MetaboliteCHEBI:29101 (ChEBI)
PLCB1 ProteinQ9NQ66 (Uniprot-TrEMBL)
PLCB2 ProteinQ00722 (Uniprot-TrEMBL)
PLCB3 ProteinQ01970 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
Ca2+ArrowR-HSA-451311 (Reactome)
Ca2+R-HSA-451311 (Reactome)
Edited Kainate

Receptor-glutamate

complex
ArrowR-HSA-451309 (Reactome)
Edited Kainate

Receptor-glutamate

complex
mim-catalysisR-HSA-451310 (Reactome)
Edited Kainate receptorsR-HSA-451309 (Reactome)
G-protein

beta-gamma:PLC beta

1/2/3
R-HSA-500717 (Reactome)
GRIK 3 homomerR-HSA-500708 (Reactome)
GRIK3 homomer glutamate complexArrowR-HSA-500708 (Reactome)
GRIK3 homomer glutamate complexR-HSA-500717 (Reactome)
GRIK3 homomer glutamate complexmim-catalysisR-HSA-500717 (Reactome)
Kainate

receptor-glutamate

complex
ArrowR-HSA-451283 (Reactome)
Kainate

receptor-glutamate

complex
mim-catalysisR-HSA-451311 (Reactome)
Kainate receptor-glutamate-Gprotein complexArrowR-HSA-500717 (Reactome)
Kainate ReceptorsR-HSA-451283 (Reactome)
L-GluR-HSA-451283 (Reactome)
L-GluR-HSA-451309 (Reactome)
L-GluR-HSA-500708 (Reactome)
Na+ArrowR-HSA-451310 (Reactome)
Na+R-HSA-451310 (Reactome)
R-HSA-451283 (Reactome) Kainate receptors bind glutamate in the ligand binding domain in the extracellular, N terminal region.
R-HSA-451309 (Reactome) Kainate receptors bind glutamate in the ligand binding domain in the extracellular, N terminal region.
R-HSA-451310 (Reactome) The activation of Kainate receptors by glutamate in the postsynaptic neuron leads to influx of Na+ ions resulting in depolarization of the postsynaptic membrane.
R-HSA-451311 (Reactome) Kainate receptors that are assembled with subunits GRIK1-5, are Ca2+ permeable if GRIK1 and GRIK2 are not edited at the Q/R or other sites.
These channels permit Ca2+ upon activation by glutamate or other agonists.
R-HSA-500708 (Reactome) Kainate receptors bind glutamate in the ligand binding domain in the extracellular, N terminal region.
R-HSA-500717 (Reactome) Kainate receptor activation activates G protein coupled receptors involving the release of Ca2+ from the intracellular stores. This activity of Kainate receptors is independent of ionic influx and regulates both glutamate release by the pyramidal neurons and gama-aminobutyric acid release by the internuerons.
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