KEGG   PATHWAY: mna04724
mna04724                    Pathway                                

Glutamatergic synapse - Miniopterus natalensis
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system(CNS). Glutamate is packaged into synaptic vesicles in the presynaptic terminal. Once released into the synaptic cleft, glutamate acts on postsynaptic ionotropic glutamate receptors (iGluRs) to mediate fast excitatory synaptic transmission. Glutamate can also act on metabotropic glutamate receptors (mGluRs) and exert a variety of modulatory effects through their coupling to G proteins and the subsequent recruitment of second messenger systems. Presynaptically localized Group II and Group III mGluRs are thought to represent the classical inhibitory autoreceptor mechanism that suppresses excess glutamate release. After its action on these receptors, glutamate can be removed from the synaptic cleft by EAATs located either on the presynaptic terminal, neighboring glial cells, or the postsynaptic neuron. In glia, glutamate is converted to glutamine, which is then transported back to the presynaptic terminal and converted back to glutamate.
Organismal Systems; Nervous system
Pathway map
mna04724  Glutamatergic synapse

Other DBs
GO: 0051966
Miniopterus natalensis [GN:mna]
107528214  SLC38A1; sodium-coupled neutral amino acid transporter 1 [KO:K14990]
107528216  SLC38A2; sodium-coupled neutral amino acid transporter 2 isoform X1 [KO:K14207]
107546205  GLS2; glutaminase liver isoform, mitochondrial isoform X1 [KO:K01425] [EC:]
107540656  GLS; glutaminase kidney isoform, mitochondrial isoform X1 [KO:K01425] [EC:]
107528546  SLC17A6; vesicular glutamate transporter 2 [KO:K12302]
107545115  SLC17A8; vesicular glutamate transporter 3 isoform X1 [KO:K12302]
107531888  SLC17A7; vesicular glutamate transporter 1 [KO:K12302]
107539897  GRIK1; glutamate receptor ionotropic, kainate 1 isoform X1 [KO:K05201]
107542766  GRIK2; glutamate receptor ionotropic, kainate 2 [KO:K05202]
107542581  GRIK3; glutamate receptor ionotropic, kainate 3 [KO:K05203]
107540623  GRIK4; glutamate receptor ionotropic, kainate 4 isoform X1 [KO:K05204]
107534236  GRIK5; glutamate receptor ionotropic, kainate 5 [KO:K05205]
107537716  GRIA1; glutamate receptor 1 isoform X1 [KO:K05197]
107527540  GRIA2; glutamate receptor 2 isoform X1 [KO:K05198]
107524995  GRIA3; glutamate receptor 3 [KO:K05199]
107532917  GRIA4; glutamate receptor 4 isoform X1 [KO:K05200]
107536149  GRIN1; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 1 [KO:K05208]
107525462  GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209]
107525331  GRIN2B; glutamate receptor ionotropic, NMDA 2B [KO:K05210]
107542924  GRIN2C; glutamate receptor ionotropic, NMDA 2C [KO:K05211]
107531815  GRIN2D; glutamate receptor ionotropic, NMDA 2D [KO:K05212]
107546596  GRIN3A; glutamate receptor ionotropic, NMDA 3A [KO:K05213]
107534564  GRIN3B; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 3B [KO:K05214]
107545505  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:]
107545813  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:]
107536108  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:]
107545969  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
107544252  DLG4; disks large homolog 4 isoform X1 [KO:K11828]
107535931  DLGAP1; disks large-associated protein 1 [KO:K15008]
107531781  SHANK1; SH3 and multiple ankyrin repeat domains protein 1 [KO:K15009]
107540356  SHANK2; SH3 and multiple ankyrin repeat domains protein 2 [KO:K15009]
107536031  SHANK3; SH3 and multiple ankyrin repeat domains protein 3 [KO:K15009]
107537975  TRPC1; short transient receptor potential channel 1 [KO:K04964]
107532400  GRM5; metabotropic glutamate receptor 5 [KO:K04604]
107539231  HOMER2; homer protein homolog 2 [KO:K15010]
107535042  HOMER1; homer protein homolog 1 isoform X1 [KO:K15010]
107535346  HOMER3; homer protein homolog 3 [KO:K15010]
107544926  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107542967  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:]
107536366  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:]
107536369  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:]
107539797  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:]
107538300  PRKCA; protein kinase C alpha type [KO:K02677] [EC:]
107544745  PRKCB; protein kinase C beta type [KO:K19662] [EC:]
107540426  PRKCG; protein kinase C gamma type [KO:K19663] [EC:]
107529142  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
107525255  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
107541588  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
107546298  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:]
107536544  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:]
107536549  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:]
107536550  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:]
107536561  cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:]
107528068  PLD2; phospholipase D2 [KO:K01115] [EC:]
107529520  PLD1; phospholipase D1 [KO:K01115] [EC:]
107533526  phospholipase D1 [KO:K01115] [EC:]
107541504  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:]
107530451  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
107529329  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
107529353  neuroendocrine secretory protein 55-like [KO:K04632]
107526004  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:]
107540528  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:]
107534062  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:]
107531740  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:]
107527242  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:]
107528232  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:]
107531029  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:]
107539500  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:]
107535777  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:]
107544336  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:]
107543188  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
107540188  GRM2; metabotropic glutamate receptor 2 [KO:K04605]
107541756  GRM3; metabotropic glutamate receptor 3 [KO:K04606]
107545631  GRM4; metabotropic glutamate receptor 4 [KO:K04607]
107529861  GRM6; LOW QUALITY PROTEIN: metabotropic glutamate receptor 6 [KO:K04608]
107534797  GRM7; metabotropic glutamate receptor 7 isoform X1 [KO:K04609]
107537364  GRM8; metabotropic glutamate receptor 8 [KO:K04610]
107545320  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
107540752  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
107545079  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
107543463  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
107540160  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
107540939  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
107544078  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
107541113  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
107546541  GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
107525867  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
107543109  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
107527185  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
107543194  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
107534609  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
107536795  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
107541861  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
107537622  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10-like [KO:K04545]
107541673  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
107541527  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7-like [KO:K04347]
107533406  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
107533363  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
107541750  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
107539173  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
107533587  ADRBK1; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:]
107533866  ADRBK2; beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:]
107537431  KCNJ3; LOW QUALITY PROTEIN: G protein-activated inward rectifier potassium channel 1 [KO:K04997]
107541038  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
107531982  SLC1A2; excitatory amino acid transporter 2 [KO:K05613]
107535429  SLC1A7; excitatory amino acid transporter 5 [KO:K05618]
107538096  SLC1A1; excitatory amino acid transporter 3 [KO:K05612]
107534309  SLC1A6; excitatory amino acid transporter 4 [KO:K05617]
107546425  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
107534931  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
107545825  SLC1A3; excitatory amino acid transporter 1 isoform X1 [KO:K05614]
107546301  GLUL; glutamine synthetase [KO:K01915] [EC:]
107529400  SLC38A3; sodium-coupled neutral amino acid transporter 3 [KO:K13576]
C00025  L-Glutamate
C00064  L-Glutamine
C00076  Calcium cation
C00165  Diacylglycerol
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
Niswender CM, Conn PJ
Metabotropic glutamate receptors: physiology, pharmacology, and disease.
Annu Rev Pharmacol Toxicol 50:295-322 (2010)
Ferraguti F, Crepaldi L, Nicoletti F
Metabotropic glutamate 1 receptor: current concepts and perspectives.
Pharmacol Rev 60:536-81 (2008)
Hermans E, Challiss RA
Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G-protein-coupled receptors.
Biochem J 359:465-84 (2001)
Kim CH, Lee J, Lee JY, Roche KW
Metabotropic glutamate receptors: phosphorylation and receptor signaling.
J Neurosci Res 86:1-10 (2008)
Meador-Woodruff JH, Clinton SM, Beneyto M, McCullumsmith RE
Molecular abnormalities of the glutamate synapse in the thalamus in schizophrenia.
Ann N Y Acad Sci 1003:75-93 (2003)
Sanacora G, Zarate CA, Krystal JH, Manji HK
Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders.
Nat Rev Drug Discov 7:426-37 (2008)
Gass JT, Olive MF
Glutamatergic substrates of drug addiction and alcoholism.
Biochem Pharmacol 75:218-65 (2008)
Palmada M, Centelles JJ
Excitatory amino acid neurotransmission. Pathways for metabolism, storage and reuptake of glutamate in brain.
Front Biosci 3:d701-18 (1998)
Schoepp DD
Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system.
J Pharmacol Exp Ther 299:12-20 (2001)
de Jong AP, Verhage M
Presynaptic signal transduction pathways that modulate synaptic transmission.
Curr Opin Neurobiol 19:245-53 (2009)
Pinheiro PS, Mulle C
Presynaptic glutamate receptors: physiological functions and mechanisms of action.
Nat Rev Neurosci 9:423-36 (2008)
Byrnes KR, Loane DJ, Faden AI
Metabotropic glutamate receptors as targets for multipotential treatment of neurological disorders.
Neurotherapeutics 6:94-107 (2009)
Conti F, Weinberg RJ
Shaping excitation at glutamatergic synapses.
Trends Neurosci 22:451-8 (1999)
Sheng M, Kim MJ
Postsynaptic signaling and plasticity mechanisms.
Science 298:776-80 (2002)
mna00020  Citrate cycle (TCA cycle)
mna04020  Calcium signaling pathway
mna04720  Long-term potentiation
mna04721  Synaptic vesicle cycle
mna04730  Long-term depression
KO pathway

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