KEGG   PATHWAY: ko04724Help
Entry
ko04724                     Pathway                                

Name
Glutamatergic synapse
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
BRITE hierarchy
Pathway map
ko04724  Glutamatergic synapse
ko04724

Ortholog table
Disease
H00606  Early infantile epileptic encephalopathy
H00749  Episodic ataxias
H00775  Familial or sporadic hemiplegic migraine
H00787  Congenital stationary night blindness (CSNB)
H00911  Dicarboxylic aminoaciduria
H00923  Congenital systemic glutamine deficiency (CSGD)
H01238  Phelan-McDermid syndrome
H01450  Obsessive-compulsive disorder (OCD)
H01827  Epileptic encephalopathy with continuous spike-waves during slow-wave sleep
H02111  Autism
Other DBs
BSID: 213811
GO: 0051966
Orthology
K14990  solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 1
K14207  solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 2
K01425  glutaminase [EC:3.5.1.2]
K12302  MFS transporter, ACS family, solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 6/7/8
K05201  glutamate receptor, ionotropic kainate 1
K05202  glutamate receptor, ionotropic kainate 2
K05203  glutamate receptor, ionotropic kainate 3
K05204  glutamate receptor, ionotropic kainate 4
K05205  glutamate receptor, ionotropic kainate 5
K05197  glutamate receptor 1
K05198  glutamate receptor 2
K05199  glutamate receptor 3
K05200  glutamate receptor 4
K05208  glutamate receptor ionotropic, NMDA 1
K05209  glutamate receptor ionotropic, NMDA 2A
K05210  glutamate receptor ionotropic, NMDA 2B
K05211  glutamate receptor ionotropic, NMDA 2C
K05212  glutamate receptor ionotropic, NMDA 2D
K05213  glutamate receptor ionotropic, NMDA 3A
K05214  glutamate receptor ionotropic, NMDA 3B
K04348  serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16]
K06268  serine/threonine-protein phosphatase 2B regulatory subunit
K11828  discs large protein 4
K15008  discs, large-associated protein 1
K15009  SH3 and multiple ankyrin repeat domains protein
K04964  transient receptor potential cation channel subfamily C member 1
K04603  metabotropic glutamate receptor 1
K04604  metabotropic glutamate receptor 5
K15010  homer
K04634  guanine nucleotide-binding protein G(q) subunit alpha
K05858  phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K02677  classical protein kinase C alpha type [EC:2.7.11.13]
K19662  classical protein kinase C beta type [EC:2.7.11.13]
K19663  classical protein kinase C gamma type [EC:2.7.11.13]
K04958  inositol 1,4,5-triphosphate receptor type 1
K04959  inositol 1,4,5-triphosphate receptor type 2
K04960  inositol 1,4,5-triphosphate receptor type 3
K16342  cytosolic phospholipase A2 [EC:3.1.1.4]
K01115  phospholipase D1/2 [EC:3.1.4.4]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04632  guanine nucleotide-binding protein G(s) subunit alpha
K08041  adenylate cyclase 1 [EC:4.6.1.1]
K08042  adenylate cyclase 2 [EC:4.6.1.1]
K08043  adenylate cyclase 3 [EC:4.6.1.1]
K08044  adenylate cyclase 4 [EC:4.6.1.1]
K08045  adenylate cyclase 5 [EC:4.6.1.1]
K08046  adenylate cyclase 6 [EC:4.6.1.1]
K08047  adenylate cyclase 7 [EC:4.6.1.1]
K08048  adenylate cyclase 8 [EC:4.6.1.1]
K08049  adenylate cyclase 9 [EC:4.6.1.1]
K04345  protein kinase A [EC:2.7.11.11]
K04605  metabotropic glutamate receptor 2/3
K04607  metabotropic glutamate receptor 4
K04608  metabotropic glutamate receptor 6/7/8
K04630  guanine nucleotide-binding protein G(i) subunit alpha
K04534  guanine nucleotide-binding protein G(o) subunit alpha
K04536  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K07825  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K04538  guanine nucleotide-binding protein subunit beta-4
K04539  guanine nucleotide-binding protein subunit beta-5
K07826  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K04540  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04347  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04547  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548  guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K00910  beta-adrenergic-receptor kinase [EC:2.7.11.15]
K04997  potassium inwardly-rectifying channel subfamily J member 3
K04344  voltage-dependent calcium channel P/Q type alpha-1A
K05613  solute carrier family 1 (glial high affinity glutamate transporter), member 2
K05618  solute carrier family 1 (glutamate transporter), member 7
K05612  solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter), member 1
K05617  solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6
K04850  voltage-dependent calcium channel L type alpha-1C
K04851  voltage-dependent calcium channel L type alpha-1D
K05614  solute carrier family 1 (glial high affinity glutamate transporter), member 3
K01915  glutamine synthetase [EC:6.3.1.2]
K13576  solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 3
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)
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

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