KEGG   PATHWAY: lav04724
Entry
lav04724                    Pathway                                

Name
Glutamatergic synapse - Loxodonta africana (African savanna elephant)
Description
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.
Class
Organismal Systems; Nervous system
Pathway map
lav04724  Glutamatergic synapse
lav04724

Other DBs
GO: 0051966
Organism
Loxodonta africana (African savanna elephant) [GN:lav]
Gene
100672492  SLC38A1; sodium-coupled neutral amino acid transporter 1 isoform X1 [KO:K14990]
100672778  SLC38A2; sodium-coupled neutral amino acid transporter 2 isoform X1 [KO:K14207]
100668982  GLS; glutaminase kidney isoform, mitochondrial isoform X4 [KO:K01425] [EC:3.5.1.2]
100673149  GLS2; glutaminase liver isoform, mitochondrial [KO:K01425] [EC:3.5.1.2]
100662164  SLC17A8; vesicular glutamate transporter 3 [KO:K12302]
100669857  SLC17A6; vesicular glutamate transporter 2 [KO:K12302]
100657804  SLC17A7; vesicular glutamate transporter 1 [KO:K12302]
100654024  GRIK1; glutamate receptor ionotropic, kainate 1 isoform X5 [KO:K05201]
100662247  GRIK2; glutamate receptor ionotropic, kainate 2 isoform X1 [KO:K05202]
100665987  GRIK3; glutamate receptor ionotropic, kainate 3 [KO:K05203]
100661187  GRIK4; glutamate receptor ionotropic, kainate 4 [KO:K05204]
100668613  GRIK5; glutamate receptor ionotropic, kainate 5 [KO:K05205]
100676565  GRIA1; glutamate receptor 1 isoform X2 [KO:K05197]
104846717  GRIA2; glutamate receptor 2 [KO:K05198]
100658980  GRIA3; glutamate receptor 3 isoform X1 [KO:K05199]
100658415  GRIA4; LOW QUALITY PROTEIN: glutamate receptor 4 [KO:K05200]
100663779  GRIN1; glutamate receptor ionotropic, NMDA 1 [KO:K05208]
100660738  GRIN2B; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 2B [KO:K05210]
100656237  GRIN2C; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 2C [KO:K05211]
100653538  GRIN2D; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 2D [KO:K05212]
100668524  GRIN3A; glutamate receptor ionotropic, NMDA 3A [KO:K05213]
100661626  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
100664832  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100677352  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111751572  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
100668807  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
100656811  DLG4; disks large homolog 4 isoform X6 [KO:K11828]
100659604  DLGAP1; LOW QUALITY PROTEIN: disks large-associated protein 1 [KO:K15008]
104847189  SH3 and multiple ankyrin repeat domains protein 3-like [KO:K15009]
100662070  SH3 and multiple ankyrin repeat domains protein 2 [KO:K15009]
100658653  SHANK1; LOW QUALITY PROTEIN: SH3 and multiple ankyrin repeat domains protein 1 [KO:K15009]
100654811  TRPC1; short transient receptor potential channel 1 isoform X1 [KO:K04964]
100676641  GRM5; LOW QUALITY PROTEIN: metabotropic glutamate receptor 5 [KO:K04604]
100672706  HOMER1; homer protein homolog 1 [KO:K15010]
100666467  HOMER3; homer protein homolog 3 [KO:K15010]
100657081  HOMER2; LOW QUALITY PROTEIN: homer protein homolog 2 [KO:K15010]
100656672  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
100670617  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
100672435  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
100668575  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100663829  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
100665537  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
100672078  PRKCB; LOW QUALITY PROTEIN: protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
100671733  PRKCG; LOW QUALITY PROTEIN: protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100665028  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
100667845  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100659666  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
111753010  PLA2G4B; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
100675131  PLA2G4D; LOW QUALITY PROTEIN: cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
100675410  PLA2G4F; LOW QUALITY PROTEIN: cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
100658490  PLA2G4A; cytosolic phospholipase A2 isoform X2 [KO:K16342] [EC:3.1.1.4]
100667057  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
100660595  PLD1; phospholipase D1 isoform X2 [KO:K01115] [EC:3.1.4.4]
100658318  PLD2; LOW QUALITY PROTEIN: phospholipase D2 [KO:K01115] [EC:3.1.4.4]
100658240  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100665157  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100655206  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
100669226  neuroendocrine secretory protein 55-like [KO:K04632]
100671072  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100673570  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100674724  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
100675525  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
100670244  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100653532  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
100653771  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100661616  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
100663448  ADCY9; LOW QUALITY PROTEIN: adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
100656966  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100674245  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100664937  GRM2; metabotropic glutamate receptor 2 [KO:K04605]
100663502  GRM3; metabotropic glutamate receptor 3 isoform X1 [KO:K04606]
100668676  GRM4; metabotropic glutamate receptor 4 [KO:K04607]
100673918  GRM6; LOW QUALITY PROTEIN: metabotropic glutamate receptor 6 [KO:K04608]
100664172  GRM7; metabotropic glutamate receptor 7 isoform X1 [KO:K04609]
100662461  GRM8; LOW QUALITY PROTEIN: metabotropic glutamate receptor 8 [KO:K04610]
100666344  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
100670234  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100667957  GNAI3; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
100658419  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
100673391  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
100677127  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
100674807  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
100669106  GNB4; LOW QUALITY PROTEIN: guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
100674665  GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539]
100668996  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 isoform X2 [KO:K07826]
100676083  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
100664179  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
100656403  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
100655407  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
100662559  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
111749727  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
111751488  GNG14; LOW QUALITY PROTEIN: putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
111750996  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
100675882  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
111749728  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
111751775  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
100666578  GRK3; beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
100671884  GRK2; beta-adrenergic receptor kinase 1 isoform X1 [KO:K00910] [EC:2.7.11.15]
100668323  KCNJ3; LOW QUALITY PROTEIN: G protein-activated inward rectifier potassium channel 1 [KO:K04997]
100655176  CACNA1A; LOW QUALITY PROTEIN: voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
100672626  SLC1A2; excitatory amino acid transporter 2 isoform X2 [KO:K05613]
100677557  SLC1A7; excitatory amino acid transporter 5 isoform X1 [KO:K05618]
100671507  SLC1A1; excitatory amino acid transporter 3 [KO:K05612]
100673388  SLC1A6; excitatory amino acid transporter 4 isoform X1 [KO:K05617]
100659992  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
100655719  SLC1A3; excitatory amino acid transporter 1 [KO:K05614]
100673871  GLUL; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
100670517  SLC38A3; sodium-coupled neutral amino acid transporter 3 isoform X1 [KO:K13576]
Compound
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
Reference
  Authors
Niswender CM, Conn PJ
  Title
Metabotropic glutamate receptors: physiology, pharmacology, and disease.
  Journal
Annu Rev Pharmacol Toxicol 50:295-322 (2010)
DOI:10.1146/annurev.pharmtox.011008.145533
Reference
  Authors
Ferraguti F, Crepaldi L, Nicoletti F
  Title
Metabotropic glutamate 1 receptor: current concepts and perspectives.
  Journal
Pharmacol Rev 60:536-81 (2008)
DOI:10.1124/pr.108.000166
Reference
  Authors
Hermans E, Challiss RA
  Title
Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G-protein-coupled receptors.
  Journal
Biochem J 359:465-84 (2001)
DOI:10.1042/bj3590465
Reference
  Authors
Kim CH, Lee J, Lee JY, Roche KW
  Title
Metabotropic glutamate receptors: phosphorylation and receptor signaling.
  Journal
J Neurosci Res 86:1-10 (2008)
DOI:10.1002/jnr.21437
Reference
  Authors
Meador-Woodruff JH, Clinton SM, Beneyto M, McCullumsmith RE
  Title
Molecular abnormalities of the glutamate synapse in the thalamus in schizophrenia.
  Journal
Ann N Y Acad Sci 1003:75-93 (2003)
DOI:10.1196/annals.1300.005
Reference
  Authors
Sanacora G, Zarate CA, Krystal JH, Manji HK
  Title
Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders.
  Journal
Nat Rev Drug Discov 7:426-37 (2008)
DOI:10.1038/nrd2462
Reference
  Authors
Gass JT, Olive MF
  Title
Glutamatergic substrates of drug addiction and alcoholism.
  Journal
Biochem Pharmacol 75:218-65 (2008)
DOI:10.1016/j.bcp.2007.06.039
Reference
PMID:9665875
  Authors
Palmada M, Centelles JJ
  Title
Excitatory amino acid neurotransmission. Pathways for metabolism, storage and reuptake of glutamate in brain.
  Journal
Front Biosci 3:d701-18 (1998)
DOI:10.2741/a314
Reference
  Authors
Schoepp DD
  Title
Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system.
  Journal
J Pharmacol Exp Ther 299:12-20 (2001)
Reference
  Authors
de Jong AP, Verhage M
  Title
Presynaptic signal transduction pathways that modulate synaptic transmission.
  Journal
Curr Opin Neurobiol 19:245-53 (2009)
DOI:10.1016/j.conb.2009.06.005
Reference
  Authors
Pinheiro PS, Mulle C
  Title
Presynaptic glutamate receptors: physiological functions and mechanisms of action.
  Journal
Nat Rev Neurosci 9:423-36 (2008)
DOI:10.1038/nrn2379
Reference
  Authors
Byrnes KR, Loane DJ, Faden AI
  Title
Metabotropic glutamate receptors as targets for multipotential treatment of neurological disorders.
  Journal
Neurotherapeutics 6:94-107 (2009)
DOI:10.1016/j.nurt.2008.10.038
Reference
  Authors
Conti F, Weinberg RJ
  Title
Shaping excitation at glutamatergic synapses.
  Journal
Trends Neurosci 22:451-8 (1999)
DOI:10.1016/S0166-2236(99)01445-9
Reference
  Authors
Sheng M, Kim MJ
  Title
Postsynaptic signaling and plasticity mechanisms.
  Journal
Science 298:776-80 (2002)
DOI:10.1126/science.1075333
Related
pathway
lav00020  Citrate cycle (TCA cycle)
lav04020  Calcium signaling pathway
lav04720  Long-term potentiation
lav04721  Synaptic vesicle cycle
lav04730  Long-term depression
KO pathway
ko04724   
LinkDB

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