KEGG   PATHWAY: oro04727
Entry
oro04727                    Pathway                                
Name
GABAergic synapse - Odobenus rosmarus divergens (Pacific walrus)
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
oro04727  GABAergic synapse
oro04727

Other DBs
GO: 0051932
Organism
Odobenus rosmarus divergens (Pacific walrus) [GN:oro]
Gene
101375244  SLC38A1; sodium-coupled neutral amino acid transporter 1 [KO:K14990]
101374755  SLC38A2; sodium-coupled neutral amino acid transporter 2 isoform X1 [KO:K14207]
101378308  GLS; glutaminase kidney isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
101370122  GLS2; glutaminase liver isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
101369025  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
101365318  GAD1; glutamate decarboxylase 1 isoform X1 [KO:K01580] [EC:4.1.1.15]
101368793  SLC32A1; vesicular inhibitory amino acid transporter [KO:K15015]
101381467  ABAT; 4-aminobutyrate aminotransferase, mitochondrial [KO:K13524] [EC:2.6.1.19 2.6.1.22]
101367195  GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175]
101367694  GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175]
101383169  GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 isoform X1 [KO:K05175]
101384124  GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 [KO:K05175]
101384663  GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 [KO:K05175]
101374508  GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 isoform X2 [KO:K05175]
101375620  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 [KO:K05181]
101367987  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181]
101382692  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 isoform X2 [KO:K05181]
101366419  GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186]
101374799  GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186]
101384321  GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 [KO:K05186]
101381192  GABRD; gamma-aminobutyric acid receptor subunit delta [KO:K05184]
101373634  GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185]
101376482  GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192]
101381014  GABRP; gamma-aminobutyric acid receptor subunit pi isoform X1 [KO:K05189]
101367408  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
101383001  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
101368668  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
101386060  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101380879  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101363254  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
101366522  HAP1; huntingtin-associated protein 1 [KO:K04647]
101368575  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
101367890  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
101374677  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
101374156  NSF; vesicle-fusing ATPase isoform X1 [KO:K06027] [EC:3.6.4.6]
101365248  TRAK2; trafficking kinesin-binding protein 2 [KO:K15374]
101386178  GPHN; gephyrin isoform X2 [KO:K15376] [EC:2.10.1.1 2.7.7.75]
101380800  SLC12A5; solute carrier family 12 member 5 isoform X1 [KO:K23967]
101362961  GABRR3; gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190]
101371998  GABRR1; gamma-aminobutyric acid receptor subunit rho-1 isoform X1 [KO:K05190]
101372494  GABRR2; gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190]
101378448  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344]
105758129  voltage-dependent N-type calcium channel subunit alpha-1B-like [KO:K04849]
101365624  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
101383514  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
101364481  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
101385947  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
101374451  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
101378598  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
101376186  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
101367568  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
101367936  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
101376297  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
101381482  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 isoform X1 [KO:K04536]
101378633  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 isoform X1 [KO:K04537]
101371845  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
101369300  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
101362117  GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539]
101366315  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
101376879  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
101369684  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
101365462  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
101363588  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
101371482  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
101370001  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
101375712  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
101379027  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
101374080  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
101368814  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7-like [KO:K04347]
101382152  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
101375999  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 isoform X1 [KO:K04548]
101386155  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
101379158  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101365382  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101368682  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
101374313  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
101380824  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101373816  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
101377421  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
101370350  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101364108  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101366647  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
101367494  SLC6A1; sodium- and chloride-dependent GABA transporter 1 [KO:K05034]
101372621  SLC6A13; sodium- and chloride-dependent GABA transporter 2 [KO:K05046]
101367789  SLC6A11; sodium- and chloride-dependent GABA transporter 3 isoform X2 [KO:K05044]
101372910  SLC6A12; sodium- and chloride-dependent betaine transporter [KO:K05045]
101380662  GLUL; glutamine synthetase isoform X1 [KO:K01915] [EC:6.3.1.2]
101367647  SLC38A3; sodium-coupled neutral amino acid transporter 3 [KO:K13576]
101376495  SLC38A5; sodium-coupled neutral amino acid transporter 5 isoform X1 [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
oro00020  Citrate cycle (TCA cycle)
oro00250  Alanine, aspartate and glutamate metabolism
oro04144  Endocytosis
oro04721  Synaptic vesicle cycle
KO pathway
ko04727   
LinkDB

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