KEGG   PATHWAY: mmu04727
Entry
mmu04727                    Pathway                                
Name
GABAergic synapse - Mus musculus (house mouse)
Description
Gamma aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the mammalian central nervous system (CNS). When released in the synaptic cleft, GABA binds to three major classes of receptors: GABAA, GABAB, and GABAC receptors. GABAA and GABAC receptors are ionotropic and mediate fast GABA responses by triggering chloride channel openings, while GABAB receptors are metabotropic and mediate slower GABA responses by activating G-proteins and influencing second messenger systems. GABAA receptors, the major sites for fast inhibitory neurotransmission in the CNS, are regulated by phosphorylation mechanisms, affecting both their functional properties and their cell surface mobility and trafficking. GABA release by the presynaptic terminal is negatively regulated by GABAB autoreceptors, and is cleared from the extracellular space by GABA transporters (GATs) located either on the presynaptic terminal or neighboring glial cells.
Class
Organismal Systems; Nervous system
Pathway map
mmu04727  GABAergic synapse
mmu04727

Other DBs
GO: 0051932
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
105727  Slc38a1; solute carrier family 38, member 1 [KO:K14990]
67760  Slc38a2; solute carrier family 38, member 2 [KO:K14207]
216456  Gls2; glutaminase 2 (liver, mitochondrial) [KO:K01425] [EC:3.5.1.2]
14660  Gls; glutaminase [KO:K01425] [EC:3.5.1.2]
14415  Gad1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
14417  Gad2; glutamic acid decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
22348  Slc32a1; solute carrier family 32 (GABA vesicular transporter), member 1 [KO:K15015]
268860  Abat; 4-aminobutyrate aminotransferase [KO:K13524] [EC:2.6.1.19 2.6.1.22]
14394  Gabra1; gamma-aminobutyric acid type A receptor subunit alpha 1 [KO:K05175]
14395  Gabra2; gamma-aminobutyric acid type A receptor subunit alpha 2 [KO:K05175]
14396  Gabra3; gamma-aminobutyric acid type A receptor subunit alpha 3 [KO:K05175]
14397  Gabra4; gamma-aminobutyric acid type A receptor subunit alpha 4 [KO:K05175]
110886  Gabra5; gamma-aminobutyric acid type A receptor subunit alpha 5 [KO:K05175]
14399  Gabra6; gamma-aminobutyric acid type A receptor subunit alpha 6 [KO:K05175]
14400  Gabrb1; gamma-aminobutyric acid type A receptor subunit beta 1 [KO:K05181]
14402  Gabrb3; GABRB3, gamma-aminobutyric acid type A receptor subunit beta 3 [KO:K05181]
14401  Gabrb2; gamma-aminobutyric acid type A receptor subunit beta 2 [KO:K05181]
14405  Gabrg1; gamma-aminobutyric acid type A receptor subunit gamma 1 [KO:K05186]
14406  Gabrg2; gamma-aminobutyric acid type A receptor, subunit gamma 2 [KO:K05186]
14407  Gabrg3; gamma-aminobutyric acid type A receptor, subunit gamma 3 [KO:K05186]
14403  Gabrd; gamma-aminobutyric acid (GABA) A receptor, subunit delta [KO:K05184]
14404  Gabre; gamma-aminobutyric acid (GABA) A receptor, subunit epsilon [KO:K05185]
57249  Gabrq; gamma-aminobutyric acid type A receptor subunit theta [KO:K05192]
216643  Gabrp; gamma-aminobutyric acid type A receptor subunit pi [KO:K05189]
18747  Prkaca; protein kinase, cAMP dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
18749  Prkacb; protein kinase, cAMP dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
20779  Src; Rous sarcoma oncogene [KO:K05704] [EC:2.7.10.2]
18750  Prkca; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
18751  Prkcb; protein kinase C, beta [KO:K19662] [EC:2.7.11.13]
18752  Prkcg; protein kinase C, gamma [KO:K19663] [EC:2.7.11.13]
15114  Hap1; huntingtin-associated protein 1 [KO:K04647]
57436  Gabarapl1; GABA type A receptor associated protein like 1 [KO:K08341]
56486  Gabarap; gamma-aminobutyric acid receptor associated protein [KO:K08341]
93739  Gabarapl2; GABA type A receptor associated protein like 2 [KO:K08341]
18195  Nsf; N-ethylmaleimide sensitive fusion protein [KO:K06027] [EC:3.6.4.6]
70827  Trak2; trafficking protein, kinesin binding 2 [KO:K15374]
227120  Plcl1; phospholipase C-like 1 [KO:K15375]
268566  Gphn; gephyrin [KO:K15376] [EC:2.10.1.1 2.7.7.75]
57138  Slc12a5; solute carrier family 12, member 5 [KO:K23967]
14408  Gabrr1; gamma-aminobutyric acid type A receptor subunit rho 1 [KO:K05190]
14409  Gabrr2; gamma-aminobutyric acid type A receptor subunit rho 2 [KO:K05190]
328699  Gabrr3; gamma-aminobutyric acid type A receptor subunit rho 3 [KO:K05190]
12286  Cacna1a; calcium channel, voltage-dependent, P/Q type, alpha 1A subunit [KO:K04344]
12287  Cacna1b; calcium channel, voltage-dependent, N type, alpha 1B subunit [KO:K04849]
12288  Cacna1c; calcium channel, voltage-dependent, L type, alpha 1C subunit [KO:K04850]
12289  Cacna1d; calcium channel, voltage-dependent, L type, alpha 1D subunit [KO:K04851]
54652  Cacna1f; calcium channel, voltage-dependent, alpha 1F subunit [KO:K04853]
12292  Cacna1s; calcium channel, voltage-dependent, L type, alpha 1S subunit [KO:K04857]
54393  Gabbr1; gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
242425  Gabbr2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
14677  Gnai1; G protein subunit alpha i1 [KO:K04630]
14679  Gnai3; G protein subunit alpha i3 [KO:K04630]
14678  Gnai2; G protein subunit alpha i2 [KO:K04630]
14681  Gnao1; guanine nucleotide binding protein, alpha O [KO:K04534]
14688  Gnb1; guanine nucleotide binding protein (G protein), beta 1 [KO:K04536]
14693  Gnb2; guanine nucleotide binding protein (G protein), beta 2 [KO:K04537]
14695  Gnb3; guanine nucleotide binding protein (G protein), beta 3 [KO:K07825]
14696  Gnb4; guanine nucleotide binding protein (G protein), beta 4 [KO:K04538]
14697  Gnb5; guanine nucleotide binding protein (G protein), beta 5 [KO:K04539]
14702  Gng2; guanine nucleotide binding protein (G protein), gamma 2 [KO:K07826]
14704  Gng3; guanine nucleotide binding protein (G protein), gamma 3 [KO:K04540]
14706  Gng4; guanine nucleotide binding protein (G protein), gamma 4 [KO:K04541]
14707  Gng5; G protein subunit gamma 5 [KO:K04542]
14708  Gng7; guanine nucleotide binding protein (G protein), gamma 7 [KO:K04543]
14709  Gng8; guanine nucleotide binding protein (G protein), gamma 8 [KO:K04544]
14700  Gng10; guanine nucleotide binding protein (G protein), gamma 10 [KO:K04545]
66066  Gng11; guanine nucleotide binding protein (G protein), gamma 11 [KO:K04546]
14701  Gng12; guanine nucleotide binding protein (G protein), gamma 12 [KO:K04347]
100503710  Gng14; G protein subunit gamma 14 [KO:K04347]
64337  Gng13; guanine nucleotide binding protein (G protein), gamma 13 [KO:K04547]
14699  Gngt1; guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 1 [KO:K04548]
14710  Gngt2; guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 2 [KO:K04549]
432530  Adcy1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
210044  Adcy2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
104111  Adcy3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
104110  Adcy4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
224129  Adcy5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
11512  Adcy6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
11513  Adcy7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
11514  Adcy8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
11515  Adcy9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
16522  Kcnj6; potassium inwardly-rectifying channel, subfamily J, member 6 [KO:K05000]
232333  Slc6a1; solute carrier family 6 (neurotransmitter transporter, GABA), member 1 [KO:K05034]
14412  Slc6a13; solute carrier family 6 (neurotransmitter transporter, GABA), member 13 [KO:K05046]
243616  Slc6a11; solute carrier family 6 (neurotransmitter transporter, GABA), member 11 [KO:K05044]
14411  Slc6a12; solute carrier family 6 (neurotransmitter transporter, betaine/GABA), member 12 [KO:K05045]
14645  Glul; glutamate-ammonia ligase [KO:K01915] [EC:6.3.1.2]
76257  Slc38a3; solute carrier family 38, member 3 [KO:K13576]
209837  Slc38a5; solute carrier family 38, member 5 [KO:K14992]
Compound
C00025  L-Glutamate
C00026  2-Oxoglutarate
C00042  Succinate
C00064  L-Glutamine
C00076  Calcium cation
C00238  Potassium cation
C00334  4-Aminobutanoate
C00575  3',5'-Cyclic AMP
C00698  Cl-
Reference
  Authors
Davis KL, Charney D, Coyle JT, Nemeroff C (ed).
  Title
Neuropsychopharmacology: The fifth generation of progress
  Journal
Lippincott Williams & Wikins (2002)
DOI:10.1002/hup.431
Reference
  Authors
Farrant M, Kaila K
  Title
The cellular, molecular and ionic basis of GABA(A) receptor signalling.
  Journal
Prog Brain Res 160:59-87 (2007)
DOI:10.1016/S0079-6123(06)60005-8
Reference
PMID:9364667
  Authors
Ben-Ari Y, Khazipov R, Leinekugel X, Caillard O, Gaiarsa JL
  Title
GABAA, NMDA and AMPA receptors: a developmentally regulated 'menage a trois'.
  Journal
Trends Neurosci 20:523-9 (1997)
DOI:10.1016/S0166-2236(97)01147-8
Reference
  Authors
Pinard A, Seddik R, Bettler B
  Title
GABAB receptors: physiological functions and mechanisms of diversity.
  Journal
Adv Pharmacol 58:231-55 (2010)
DOI:10.1016/S1054-3589(10)58010-4
Reference
  Authors
Chalifoux JR, Carter AG
  Title
GABAB receptor modulation of synaptic function.
  Journal
Curr Opin Neurobiol 21:339-44 (2011)
DOI:10.1016/j.conb.2011.02.004
Reference
  Authors
Padgett CL, Slesinger PA
  Title
GABAB receptor coupling to G-proteins and ion channels.
  Journal
Adv Pharmacol 58:123-47 (2010)
DOI:10.1016/S1054-3589(10)58006-2
Reference
  Authors
Emson PC
  Title
GABA(B) receptors: structure and function.
  Journal
Prog Brain Res 160:43-57 (2007)
DOI:10.1016/S0079-6123(06)60004-6
Reference
  Authors
Kornau HC
  Title
GABA(B) receptors and synaptic modulation.
  Journal
Cell Tissue Res 326:517-33 (2006)
DOI:10.1007/s00441-006-0264-7
Reference
  Authors
Jacob TC, Moss SJ, Jurd R
  Title
GABA(A) receptor trafficking and its role in the dynamic modulation of neuronal inhibition.
  Journal
Nat Rev Neurosci 9:331-43 (2008)
DOI:10.1038/nrn2370
Reference
  Authors
Kneussel M
  Title
Dynamic regulation of GABA(A) receptors at synaptic sites.
  Journal
Brain Res Brain Res Rev 39:74-83 (2002)
DOI:10.1016/S0165-0173(02)00159-5
Reference
  Authors
Luscher B, Fuchs T, Kilpatrick CL
  Title
GABAA receptor trafficking-mediated plasticity of inhibitory synapses.
  Journal
Neuron 70:385-409 (2011)
DOI:10.1016/j.neuron.2011.03.024
Reference
  Authors
Arancibia-Carcamo IL, Kittler JT
  Title
Regulation of GABA(A) receptor membrane trafficking and synaptic localization.
  Journal
Pharmacol Ther 123:17-31 (2009)
DOI:10.1016/j.pharmthera.2009.03.012
Reference
  Authors
Bak LK, Schousboe A, Waagepetersen HS
  Title
The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer.
  Journal
J Neurochem 98:641-53 (2006)
DOI:10.1111/j.1471-4159.2006.03913.x
Reference
  Authors
Conti F, Minelli A, Melone M
  Title
GABA transporters in the mammalian cerebral cortex: localization, development and pathological implications.
  Journal
Brain Res Brain Res Rev 45:196-212 (2004)
DOI:10.1016/j.brainresrev.2004.03.003
Reference
  Authors
Brambilla P, Perez J, Barale F, Schettini G, Soares JC
  Title
GABAergic dysfunction in mood disorders.
  Journal
Mol Psychiatry 8:721-37, 715 (2003)
DOI:10.1038/sj.mp.4001362
Reference
  Authors
Chebib M, Johnston GA
  Title
GABA-Activated ligand gated ion channels: medicinal chemistry and molecular biology.
  Journal
J Med Chem 43:1427-47 (2000)
DOI:10.1021/jm9904349
Related
pathway
mmu00020  Citrate cycle (TCA cycle)
mmu00250  Alanine, aspartate and glutamate metabolism
mmu04144  Endocytosis
mmu04721  Synaptic vesicle cycle
KO pathway
ko04727   
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