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
Glutamatergic synapse
ko04724

All organismsOrtholog table
Disease
H00577  
Syndromic X-linked mental retardation with epilepsy or seizures
H00749  
Episodic ataxias
H00768  
Nonsyndromic autosomal recessive mental retardation (NS-ARMR)
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
Other DBs
BSID: 
GO: 
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 [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)
Reference
  Authors
Ferraguti F, Crepaldi L, Nicoletti F
  Title
Metabotropic glutamate 1 receptor: current concepts and perspectives.
  Journal
Pharmacol Rev 60:536-81 (2008)
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)
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)
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)
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)
Reference
  Authors
Gass JT, Olive MF
  Title
Glutamatergic substrates of drug addiction and alcoholism.
  Journal
Biochem Pharmacol 75:218-65 (2008)
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)
Reference
  Authors
Pinheiro PS, Mulle C
  Title
Presynaptic glutamate receptors: physiological functions and mechanisms of action.
  Journal
Nat Rev Neurosci 9:423-36 (2008)
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)
Reference
  Authors
Conti F, Weinberg RJ
  Title
Shaping excitation at glutamatergic synapses.
  Journal
Trends Neurosci 22:451-8 (1999)
Reference
  Authors
Sheng M, Kim MJ
  Title
Postsynaptic signaling and plasticity mechanisms.
  Journal
Science 298:776-80 (2002)

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