KEGG   PATHWAY: oor04727
Entry
oor04727                    Pathway                                
Name
GABAergic synapse - Orcinus orca (killer whale)
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
oor04727  GABAergic synapse
oor04727

Other DBs
GO: 0051932
Organism
Orcinus orca (killer whale) [GN:oor]
Gene
101269256  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
101269282  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
101270085  GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X2 [KO:K04539]
101270664  SLC38A5; sodium-coupled neutral amino acid transporter 5 isoform X4 [KO:K14992]
101270764  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
101271265  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
101271719  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101271724  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
101272028  GLS; glutaminase kidney isoform, mitochondrial isoform X2 [KO:K01425] [EC:3.5.1.2]
101272376  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101272416  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B isoform X1 [KO:K04849]
101272599  ABAT; 4-aminobutyrate aminotransferase, mitochondrial isoform X1 [KO:K13524] [EC:2.6.1.19 2.6.1.22]
101272740  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X7 [KO:K04850]
101273023  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
101273171  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101273592  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101273911  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101274009  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
101275089  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:2.7.10.2]
101275185  SLC6A11; sodium- and chloride-dependent GABA transporter 3 [KO:K05044]
101275262  GABRP; gamma-aminobutyric acid receptor subunit pi isoform X1 [KO:K05189]
101275416  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
101275449  SLC6A1; sodium- and chloride-dependent GABA transporter 1 [KO:K05034]
101275783  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344]
101276063  [KO:K04542]
101276240  SLC38A3; sodium-coupled neutral amino acid transporter 3 [KO:K13576]
101276350  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101276371  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
101276418  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
101276500  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
101276560  HAP1; huntingtin-associated protein 1 [KO:K04647]
101276749  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
101276847  GABRR3; LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190]
101277002  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101277158  GABRE; gamma-aminobutyric acid receptor subunit epsilon isoform X1 [KO:K05185]
101277343  GNB4; guanine nucleotide-binding protein subunit beta-4 isoform X1 [KO:K04538]
101277397  GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 isoform X4 [KO:K05175]
101277471  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
101277502  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 [KO:K05181]
101277504  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
101277644  GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192]
101277678  GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 isoform X1 [KO:K05175]
101277753  GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 [KO:K05175]
101278238  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 [KO:K05181]
101278335  SLC12A5; solute carrier family 12 member 5 isoform X1 [KO:K23967]
101278368  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
101278543  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
101278551  GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 isoform X1 [KO:K05175]
101278646  GABRG3; LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186]
101279126  GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 [KO:K05186]
101279144  SLC32A1; vesicular inhibitory amino acid transporter isoform X1 [KO:K15015]
101279405  NSF; vesicle-fusing ATPase isoform X2 [KO:K06027] [EC:3.6.4.6]
101279847  GPHN; gephyrin isoform X10 [KO:K15376] [EC:2.10.1.1 2.7.7.75]
101280073  SLC38A2; sodium-coupled neutral amino acid symporter 2 isoform X1 [KO:K14207]
101280405  GLS2; glutaminase liver isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
101280514  SLC6A13; sodium- and chloride-dependent GABA transporter 2 isoform X1 [KO:K05046]
101280752  SLC38A1; sodium-coupled neutral amino acid symporter 1 isoform X1 [KO:K14990]
101280755  [KO:K08341]
101281199  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X11 [KO:K04853]
101281533  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
101281538  TRAK2; trafficking kinesin-binding protein 2 [KO:K15374]
101281654  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101282575  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
101282693  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
101282983  GABRD; gamma-aminobutyric acid receptor subunit delta [KO:K05184]
101283178  ADCY5; adenylate cyclase type 5 isoform X2 [KO:K08045] [EC:4.6.1.1]
101283651  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
101284566  [KO:K04534]
101286052  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
101286207  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101287027  GABRR2; gamma-aminobutyric acid receptor subunit rho-2 isoform X1 [KO:K05190]
101287054  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X2 [KO:K04615]
101287285  GABRR1; gamma-aminobutyric acid receptor subunit rho-1 isoform X1 [KO:K05190]
101287429  PLCL1; inactive phospholipase C-like protein 1 [KO:K15375]
101287620  GAD1; glutamate decarboxylase 1 isoform X1 [KO:K01580] [EC:4.1.1.15]
101288065  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
101288727  GLUL; glutamine synthetase isoform X2 [KO:K01915] [EC:6.3.1.2]
101288822  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181]
101289403  GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 isoform X2 [KO:K05175]
101289643  GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 isoform X1 [KO:K05175]
101289858  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
101290044  GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186]
101290360  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
105747741  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
117197734  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
117197871  [KO:K04542]
117198830  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
117201513  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
117201789  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
117202102  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
117202637  [KO:K04545]
117202794  [KO:K04542]
125960266  SLC6A12; sodium- and chloride-dependent betaine transporter [KO:K05045]
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
oor00020  Citrate cycle (TCA cycle)
oor00250  Alanine, aspartate and glutamate metabolism
oor04144  Endocytosis
oor04721  Synaptic vesicle cycle
KO pathway
ko04727   

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