Activation of kainate receptors upon glutamate binding (Homo sapiens)

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Community: Reactome Comment: Reactome version 75 The current version of this pathway has been approved by the Reactome curation team (tagged by Reactome Team).

Fix interactions Comment: 6 out of 25 lines are not properly connected. Please help improving this pathway by connecting the ends of interactions to nodes.

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Bibliography

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

External references

DataNodes

Name	Type	Database reference	Comment
CALM1	Protein	P0DP23 (Uniprot-TrEMBL)
Ca2+	Metabolite	CHEBI:29108 (ChEBI)
Cl-	Metabolite	CHEBI:17996 (ChEBI)
DLG1	Protein	Q12959 (Uniprot-TrEMBL)
DLG3	Protein	Q92796 (Uniprot-TrEMBL)
DLG4	Protein	P78352 (Uniprot-TrEMBL)
Edited GRIK 1 (GluR5)	Protein	P39086 (Uniprot-TrEMBL)	Glutamine at position 636 is replaced by arginine in an editing step which occurs posttranscriptionally.
Edited GRIK2 (GluR6)	Protein	Q13002 (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	Complex	R-HSA-451304 (Reactome)
Edited Kainate receptors	Complex	R-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	Complex	R-HSA-398037 (Reactome)
GNB1	Protein	P62873 (Uniprot-TrEMBL)
GNB2	Protein	P62879 (Uniprot-TrEMBL)
GNB3	Protein	P16520 (Uniprot-TrEMBL)
GNB4	Protein	Q9HAV0 (Uniprot-TrEMBL)
GNB5	Protein	O14775 (Uniprot-TrEMBL)
GNG10	Protein	P50151 (Uniprot-TrEMBL)
GNG11	Protein	P61952 (Uniprot-TrEMBL)
GNG12	Protein	Q9UBI6 (Uniprot-TrEMBL)
GNG13	Protein	Q9P2W3 (Uniprot-TrEMBL)
GNG2	Protein	P59768 (Uniprot-TrEMBL)
GNG3	Protein	P63215 (Uniprot-TrEMBL)
GNG4	Protein	P50150 (Uniprot-TrEMBL)
GNG5	Protein	P63218 (Uniprot-TrEMBL)
GNG7	Protein	O60262 (Uniprot-TrEMBL)
GNG8	Protein	Q9UK08 (Uniprot-TrEMBL)
GNGT1	Protein	P63211 (Uniprot-TrEMBL)
GNGT2	Protein	O14610 (Uniprot-TrEMBL)
GRIK 3 homomer	Complex	R-HSA-450196 (Reactome)
GRIK1	Protein	P39086 (Uniprot-TrEMBL)
GRIK2	Protein	Q13002 (Uniprot-TrEMBL)
GRIK3	Protein	Q13003 (Uniprot-TrEMBL)
GRIK3 homomer glutamate complex	Complex	R-HSA-500705 (Reactome)
GRIK4	Protein	Q16099 (Uniprot-TrEMBL)
GRIK5	Protein	Q16478 (Uniprot-TrEMBL)
Kainate receptor-glutamate complex	Complex	R-HSA-451281 (Reactome)
Kainate receptor-glutamate-Gprotein complex	Complex	R-HSA-500703 (Reactome)
Kainate Receptors	Complex	R-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	Metabolite	CHEBI:29985 (ChEBI)
L-Glu	Metabolite	CHEBI:29985 (ChEBI)
NCALD	Protein	P61601 (Uniprot-TrEMBL)
Na+	Metabolite	CHEBI:29101 (ChEBI)
PLCB1	Protein	Q9NQ66 (Uniprot-TrEMBL)
PLCB2	Protein	Q00722 (Uniprot-TrEMBL)
PLCB3	Protein	Q01970 (Uniprot-TrEMBL)

Annotated Interactions

Source	Target	Type	Database reference	Comment
	Ca2+	Arrow	R-HSA-451311 (Reactome)
Ca2+			R-HSA-451311 (Reactome)
	Edited Kainate Receptor-glutamate complex	Arrow	R-HSA-451309 (Reactome)
Edited Kainate Receptor-glutamate complex		mim-catalysis	R-HSA-451310 (Reactome)
Edited Kainate receptors			R-HSA-451309 (Reactome)
G-protein beta-gamma:PLC beta 1/2/3			R-HSA-500717 (Reactome)
GRIK 3 homomer			R-HSA-500708 (Reactome)
	GRIK3 homomer glutamate complex	Arrow	R-HSA-500708 (Reactome)
GRIK3 homomer glutamate complex			R-HSA-500717 (Reactome)
GRIK3 homomer glutamate complex		mim-catalysis	R-HSA-500717 (Reactome)
	Kainate receptor-glutamate complex	Arrow	R-HSA-451283 (Reactome)
Kainate receptor-glutamate complex		mim-catalysis	R-HSA-451311 (Reactome)
	Kainate receptor-glutamate-Gprotein complex	Arrow	R-HSA-500717 (Reactome)
Kainate Receptors			R-HSA-451283 (Reactome)
L-Glu			R-HSA-451283 (Reactome)
L-Glu			R-HSA-451309 (Reactome)
L-Glu			R-HSA-500708 (Reactome)
	Na+	Arrow	R-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.