KEGG   PATHWAY: bta04727
Entry
bta04727                    Pathway                                
Name
GABAergic synapse - Bos taurus (cow)
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
bta04727  GABAergic synapse
bta04727

Other DBs
GO: 0051932
Organism
Bos taurus (cow) [GN:bta]
Gene
100125276  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
100301361  SLC32A1; vesicular inhibitory amino acid transporter [KO:K15015]
100337204  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
104968964  [KO:K04542]
280969  ABAT; 4-aminobutyrate aminotransferase, mitochondrial [KO:K13524] [EC:2.6.1.19 2.6.1.22]
281199  GLUL; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
281201  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
281202  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
281203  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
281204  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
281601  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
281603  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
281790  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
281791  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
281792  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
281796  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
281797  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
282001  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
282002  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
282236  GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 precursor [KO:K05175]
282237  GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 precursor [KO:K05175]
282238  GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 precursor [KO:K05175]
282239  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 precursor [KO:K05181]
282240  GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 precursor [KO:K05186]
282322  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
282323  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
282325  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
282410  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849]
282531  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
282648  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
286850  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
287018  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
326576  SLC38A3; sodium-coupled neutral amino acid transporter 3 [KO:K13576]
327715  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
338044  SLC38A2; sodium-coupled neutral amino acid symporter 2 [KO:K14207]
338472  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
407118  SLC6A1; sodium- and chloride-dependent GABA transporter 1 [KO:K05034]
408013  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
408015  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
504457  NSF; vesicle-fusing ATPase [KO:K06027] [EC:3.6.4.6]
505740  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
508711  GABRD; gamma-aminobutyric acid receptor subunit delta precursor [KO:K05184]
509779  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
509936  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
510157  SLC12A5; solute carrier family 12 member 5 [KO:K23967]
510708  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
511812  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
512459  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
512495  SLC38A5; sodium-coupled neutral amino acid transporter 5 [KO:K14992]
513340  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
513785  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform 2 precursor [KO:K04615]
514339  SLC6A12; sodium- and chloride-dependent betaine transporter [KO:K05045]
517006  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
517040  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
517459  GABRP; gamma-aminobutyric acid receptor subunit pi precursor [KO:K05189]
517552  GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
520166  GABRR3; gamma-aminobutyric acid receptor subunit rho-3 precursor [KO:K05190]
520743  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
521180  GABRR1; gamma-aminobutyric acid receptor subunit rho-1 [KO:K05190]
522099  GABRR2; gamma-aminobutyric acid receptor subunit rho-2 precursor [KO:K05190]
523515  GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 precursor [KO:K05175]
523784  SLC6A13; sodium- and chloride-dependent GABA transporter 2 [KO:K05046]
523970  TRAK2; trafficking kinesin-binding protein 2 [KO:K15374]
524115  GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185]
525335  GLS; glutaminase kidney isoform, mitochondrial [KO:K01425] [EC:3.5.1.2]
525482  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
525962  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
527180  GABRQ; gamma-aminobutyric acid receptor subunit theta precursor [KO:K05192]
527491  SLC38A1; sodium-coupled neutral amino acid symporter 1 [KO:K14990]
529425  GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
529488  [KO:K01580] [EC:4.1.1.15]
529593  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 precursor [KO:K05181]
535017  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
535194  GPHN; gephyrin isoform X7 [KO:K15376] [EC:2.10.1.1 2.7.7.75]
535365  GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
535603  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
535742  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
537873  PLCL1; inactive phospholipase C-like protein 1 [KO:K15375]
539194  GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175]
539521  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
539561  GLS2; glutaminase liver isoform, mitochondrial [KO:K01425] [EC:3.5.1.2]
540657  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 precursor [KO:K05181]
613670  GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 isoform X1 [KO:K05186]
613930  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
615885  GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 precursor [KO:K05186]
616071  SLC6A11; sodium- and chloride-dependent GABA transporter 3 [KO:K05044]
618399  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
618422  HAP1; LOW QUALITY PROTEIN: huntingtin-associated protein 1 [KO:K04647]
618470  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
780973  GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 precursor [KO:K05175]
788151  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
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
PMID:17499109
  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
PMID:20655485
  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
PMID:21376567
  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
PMID:20655481
  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
PMID:17499108
  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
PMID:16932937
  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
PMID:18382465
  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
PMID:12086709
  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
PMID:21555068
  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
PMID:19374920
  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
PMID:16787421
  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
PMID:15210304
  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
PMID:12888801
  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
PMID:10780899
  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
bta00020  Citrate cycle (TCA cycle)
bta00250  Alanine, aspartate and glutamate metabolism
bta04144  Endocytosis
bta04721  Synaptic vesicle cycle
KO pathway
ko04727   

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