KEGG   PATHWAY: oas04727
Entry
oas04727                    Pathway                                
Name
GABAergic synapse - Ovis aries (sheep)
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
oas04727  GABAergic synapse
oas04727

Other DBs
GO: 0051932
Organism
Ovis aries (sheep) [GN:oas]
Gene
101112470  SLC38A1; sodium-coupled neutral amino acid symporter 1 isoform X1 [KO:K14990]
101112042  SLC38A2; sodium-coupled neutral amino acid symporter 2 isoform X1 [KO:K14207]
101122583  GLS; glutaminase kidney isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
101107269  GLS2; glutaminase liver isoform, mitochondrial isoform X2 [KO:K01425] [EC:3.5.1.2]
101106448  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
101117810  glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
101117393  glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
101105268  SLC32A1; vesicular inhibitory amino acid transporter [KO:K15015]
101105462  ABAT; 4-aminobutyrate aminotransferase, mitochondrial [KO:K13524] [EC:2.6.1.19 2.6.1.22]
101113565  GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 [KO:K05175]
101121776  GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 [KO:K05175]
101117503  GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 isoform X1 [KO:K05175]
101117759  GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175]
101121265  GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 isoform X1 [KO:K05175]
101115159  GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175]
100913155  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 precursor [KO:K05181]
101122358  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 [KO:K05181]
101114905  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 isoform X1 [KO:K05181]
101118526  GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186]
101121012  GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 [KO:K05186]
101108521  GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186]
101122539  GABRD; gamma-aminobutyric acid receptor subunit delta isoform X1 [KO:K05184]
101106150  GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185]
101113305  GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192]
101106625  GABRP; gamma-aminobutyric acid receptor subunit pi isoform X1 [KO:K05189]
443094  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101108785  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101103084  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
101110074  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101118410  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101116423  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
121820619  HAP1; LOW QUALITY PROTEIN: huntingtin-associated protein 1 [KO:K04647]
101118285  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
101118469  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
101117406  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 isoform X2 [KO:K08341]
101120344  NSF; vesicle-fusing ATPase isoform X6 [KO:K06027] [EC:3.6.4.6]
101108286  TRAK2; trafficking kinesin-binding protein 2 isoform X1 [KO:K15374]
101102372  PLCL1; inactive phospholipase C-like protein 1 isoform X1 [KO:K15375]
101112228  GPHN; gephyrin isoform X9 [KO:K15376] [EC:2.10.1.1 2.7.7.75]
101114128  SLC12A5; solute carrier family 12 member 5 isoform X3 [KO:K23967]
101104110  GABRR3; gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190]
101110852  gamma-aminobutyric acid receptor subunit rho-2 isoform X2 [KO:K05190]
101114365  gamma-aminobutyric acid receptor subunit rho-1 [KO:K05190]
101120920  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344]
101122774  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849]
101116562  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X6 [KO:K04850]
101106371  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X9 [KO:K04851]
101104552  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
101108767  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
101110007  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
101103544  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X1 [KO:K04615]
101103693  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
101116393  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
100302341  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101119495  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
101104166  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 isoform X2 [KO:K04536]
101102864  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
101110493  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
101108976  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
101106267  GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539]
101106689  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
101114066  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
101114927  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
101110631  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
105611474  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
101116593  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
114112926  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
100192421  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
106991180  GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
101115838  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
101112183  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
101114097  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 isoform X1 [KO:K04548]
105608415  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
101117327  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
101102089  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101108203  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
101119139  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
105602258  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101105735  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
101112667  ADCY7; adenylate cyclase type 7 isoform X7 [KO:K08047] [EC:4.6.1.1]
101121944  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101122401  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101117719  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
101121462  SLC6A1; sodium- and chloride-dependent GABA transporter 1 [KO:K05034]
101119630  SLC6A13; sodium- and chloride-dependent GABA transporter 2 isoform X2 [KO:K05046]
101105536  SLC6A11; sodium- and chloride-dependent GABA transporter 3 [KO:K05044]
101114770  SLC6A12; sodium- and chloride-dependent betaine transporter isoform X1 [KO:K05045]
101102999  GLUL; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
101116182  SLC38A3; sodium-coupled neutral amino acid transporter 3 isoform X2 [KO:K13576]
101113465  SLC38A5; sodium-coupled neutral amino acid transporter 5 isoform X3 [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
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
oas00020  Citrate cycle (TCA cycle)
oas00250  Alanine, aspartate and glutamate metabolism
oas04144  Endocytosis
oas04721  Synaptic vesicle cycle
KO pathway
ko04727   
LinkDB

DBGET integrated database retrieval system