KEGG   PATHWAY: rno04724
Entry
rno04724                    Pathway                                
Name
Glutamatergic synapse - Rattus norvegicus (rat)
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
rno04724  Glutamatergic synapse
rno04724

Other DBs
GO: 0051966
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
114117  Gng3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
114118  Gng4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
114119  Gng10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
114120  Gng12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116638  Slc17a7; vesicular glutamate transporter 1 [KO:K12302]
170567  Slc38a1; sodium-coupled neutral amino acid symporter 1 [KO:K14990]
170796  Grin3b; glutamate receptor ionotropic, NMDA 3B precursor [KO:K05214]
171093  Shank2; SH3 and multiple ankyrin repeat domains protein 2 isoform d [KO:K15009]
171378  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
191573  Grin3a; glutamate receptor ionotropic, NMDA 3A isoform 1 precursor [KO:K05213]
192268  Gls2; glutaminase liver isoform, mitochondrial isoform 1 [KO:K01425] [EC:3.5.1.2]
24239  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
24398  Gls; glutaminase kidney isoform, mitochondrial isoform a [KO:K01425] [EC:3.5.1.2]
24400  Gnb1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
24406  Grik4; glutamate receptor ionotropic, kainate 4 precursor [KO:K05204]
24407  Grik5; glutamate receptor ionotropic, kainate 5 precursor [KO:K05205]
24408  Grin1; glutamate receptor ionotropic, NMDA 1 isoform 1a precursor [KO:K05208]
24409  Grin2a; glutamate receptor ionotropic, NMDA 2A precursor [KO:K05209]
24410  Grin2b; glutamate receptor ionotropic, NMDA 2B precursor [KO:K05210]
24411  Grin2c; glutamate receptor ionotropic, NMDA 2C [KO:K05211]
24412  Grin2d; glutamate receptor ionotropic, NMDA 2D precursor [KO:K05212]
24414  Grm1; metabotropic glutamate receptor 1 isoform alpha precursor [KO:K04603]
24415  Grm2; metabotropic glutamate receptor 2 precursor [KO:K04605]
24416  Grm3; metabotropic glutamate receptor 3 precursor [KO:K04606]
24417  Grm4; metabotropic glutamate receptor 4 precursor [KO:K04607]
24418  Grm5; metabotropic glutamate receptor 5 precursor [KO:K04604]
24419  Grm6; metabotropic glutamate receptor 6 precursor [KO:K04608]
245986  Gng8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
24653  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
24674  Ppp3ca; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
24675  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
24681  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
24957  Glul; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
25096  Pld1; phospholipase D1 isoform 2 [KO:K01115] [EC:3.1.4.4]
25097  Pld2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
25238  Grk2; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
25262  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform 3 [KO:K04958]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:4.6.1.1]
252919  Slc38a3; sodium-coupled neutral amino acid transporter 3 [KO:K13576]
25372  Grk3; G protein-coupled receptor kinase 3 [KO:K00910] [EC:2.7.11.15]
25398  Cacna1a; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
25550  Slc1a1; excitatory amino acid transporter 3 [KO:K05612]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
25643  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
25679  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
25686  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
266767  Slc17a8; vesicular glutamate transporter 3 [KO:K12302]
280670  Lzts3; leucine zipper putative tumor suppressor 3 [KO:K26472]
29241  Adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
29482  Slc1a2; excitatory amino acid transporter 2 isoform a [KO:K05613]
29483  Slc1a3; excitatory amino acid transporter 1 isoform 1 [KO:K05614]
29495  Dlg4; disks large homolog 4 [KO:K11828]
294962  Gnb4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
29546  Homer1; homer protein homolog 1 [KO:K15010]
29547  Homer2; homer protein homolog 2 [KO:K15010]
29548  Homer3; homer protein homolog 3 [KO:K15010]
29559  Grik1; glutamate receptor ionotropic, kainate 1 isoform 1 precursor [KO:K05201]
296091  Pla2g4e; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
29627  Gria2; glutamate receptor 2 isoform 2 precursor [KO:K05198]
29628  Gria3; glutamate receptor 3 isoform 2 precursor [KO:K05199]
29629  Gria4; glutamate receptor 4 isoform 2 precursor [KO:K05200]
29642  Slc38a2; sodium-coupled neutral amino acid symporter 2 [KO:K14207]
29716  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
29748  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
29749  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
298521  Grik3; glutamate receptor ionotropic, kainate 3 isoform 1 precursor [KO:K05203]
302950  Adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
305509  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
311341  Pla2g4b; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
366432  Slc1a7; excitatory amino acid transporter 5 [KO:K05618]
50592  Gria1; glutamate receptor 1 precursor [KO:K05197]
50599  Kcnj3; G protein-activated inward rectifier potassium channel 1 [KO:K04997]
50664  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform B [KO:K04534]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
54223  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
54257  Grik2; glutamate receptor ionotropic, kainate 2 precursor [KO:K05202]
58979  Gng7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
59312  Shank3; SH3 and multiple ankyrin repeat domains protein 3 [KO:K15009]
60449  Gnb3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
60590  Grm8; metabotropic glutamate receptor 8 precursor [KO:K04610]
64199  Gng11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
64508  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
65040  Dlgap1; disks large-associated protein 1 isoform 2 [KO:K15008]
680149  Gngt1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
685451  Gng13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
685513  Gng14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
690825  Gngt2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
691810  Pla2g4c; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
691905  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
691907  Pla2g4f; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
78957  Shank1; SH3 and multiple ankyrin repeat domains protein 1 [KO:K15009]
79218  Gng5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
80850  Gng2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
81664  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
81667  Gnb2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
81672  Grm7; metabotropic glutamate receptor 7 precursor [KO:K04609]
81678  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
83579  Gnb5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
84012  Slc1a6; excitatory amino acid transporter 4 [KO:K05617]
84420  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
84487  Slc17a6; vesicular glutamate transporter 2 [KO:K12302]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
89791  Ncdn; neurochondrin [KO:K27819]
89821  Trpc1; short transient receptor potential channel 1 isoform 2 [KO:K04964]
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
PMID:20055706
  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
PMID:19112153
  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
PMID:11672421
  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
PMID:17663464
  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
PMID:14684436
  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
PMID:18425072
  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
PMID:17706608
  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
PMID:11561058
  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
PMID:19559598
  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
PMID:18464791
  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
PMID:19110202
  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
PMID:10481192
  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
PMID:12399578
  Authors
Sheng M, Kim MJ
  Title
Postsynaptic signaling and plasticity mechanisms.
  Journal
Science 298:776-80 (2002)
DOI:10.1126/science.1075333
Related
pathway
rno00020  Citrate cycle (TCA cycle)
rno04020  Calcium signaling pathway
rno04720  Long-term potentiation
rno04721  Synaptic vesicle cycle
rno04730  Long-term depression
KO pathway
ko04724   

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