KEGG PATHWAY: ko04724

PATHWAY: ko04724

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

Pathway map

ko04724

Glutamatergic synapse

Drug

D02546

Kainic acid hydrate (JP18)

Other DBs

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

K04606

metabotropic glutamate receptor 3

K04607

metabotropic glutamate receptor 4

K04608

metabotropic glutamate receptor 6

K04609

metabotropic glutamate receptor 7

K04610

metabotropic glutamate receptor 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 glutamate/aspartate 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

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

ko00020

Citrate cycle (TCA cycle)

ko04020

Calcium signaling pathway

ko04720

Long-term potentiation

ko04721

Synaptic vesicle cycle

ko04730

Long-term depression

All links

Gene (88)   
   KEGG ORTHOLOGY (88)   
All databases (88)   

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