KEGG   PATHWAY: uar04727
Entry
uar04727                    Pathway                                
Name
GABAergic synapse - Ursus americanus (American black bear)
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
uar04727  GABAergic synapse
uar04727

Other DBs
GO: 0051932
Organism
Ursus americanus (American black bear) [GN:uar]
Gene
123794824  SLC38A1; sodium-coupled neutral amino acid transporter 1 isoform X1 [KO:K14990]
123794823  SLC38A2; sodium-coupled neutral amino acid transporter 2 isoform X1 [KO:K14207]
123787244  GLS2; glutaminase liver isoform, mitochondrial [KO:K01425] [EC:3.5.1.2]
123798146  GLS; glutaminase kidney isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
123787432  glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
123780849  GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
123778151  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
123796917  SLC32A1; vesicular inhibitory amino acid transporter [KO:K15015]
123783654  ABAT; 4-aminobutyrate aminotransferase, mitochondrial [KO:K13524] [EC:2.6.1.19 2.6.1.22]
123786534  GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 [KO:K05175]
123788562  GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175]
123788631  GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175]
123804037  GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 isoform X1 [KO:K05175]
123804077  GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 [KO:K05175]
123790821  GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175]
123788560  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181]
123790822  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 [KO:K05181]
123788563  GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186]
123804041  GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 [KO:K05186]
123790746  GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186]
123796119  GABRD; gamma-aminobutyric acid receptor subunit delta isoform X1 [KO:K05184]
123787685  GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185]
123786529  GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192]
123788634  gamma-aminobutyric acid receptor subunit pi [KO:K05189]
123801768  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
123795272  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
123796968  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
123803224  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
123778823  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
123786995  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
123781927  HAP1; huntingtin-associated protein 1 [KO:K04647]
123792166  LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor-associated protein [KO:K08341]
123781641  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
123791319  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
123803251  NSF; vesicle-fusing ATPase [KO:K06027] [EC:3.6.4.6]
123798202  TRAK2; trafficking kinesin-binding protein 2 isoform X1 [KO:K15374]
123798172  PLCL1; inactive phospholipase C-like protein 1 isoform X1 [KO:K15375]
123800711  GPHN; gephyrin isoform X1 [KO:K15376] [EC:2.10.1.1 2.7.7.75]
123797064  SLC12A5; solute carrier family 12 member 5 [KO:K23967]
123798562  GABRR2; gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190]
123798601  GABRR1; gamma-aminobutyric acid receptor subunit rho-1 isoform X1 [KO:K05190]
123784331  GABRR3; LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190]
123801736  CACNA1A; LOW QUALITY PROTEIN: voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
123796292  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B isoform X1 [KO:K04849]
123777895  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
123798762  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
123797184  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
123785763  CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
123781213  GABBR2; LOW QUALITY PROTEIN: gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
123796436  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
123795104  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
123789354  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
123798684  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
123798421  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
123796116  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
123777259  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
123781583  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
123786411  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
123801797  GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539]
123800611  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
123789819  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
123783123  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
123787748  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542]
123795269  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
123793984  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
123778756  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
123803383  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
123776695  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10-like [KO:K04545]
123789281  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
123795327  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
123777697  GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
123783660  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
123789282  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
123802847  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
123789481  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
123791264  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
123799951  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
123795737  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
123802178  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
123794794  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
123798393  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
123801897  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
123783548  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
123802678  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
123799214  SLC6A1; sodium- and chloride-dependent GABA transporter 1 [KO:K05034]
123777666  SLC6A13; sodium- and chloride-dependent GABA transporter 2 isoform X1 [KO:K05046]
123799213  SLC6A11; sodium- and chloride-dependent GABA transporter 3 [KO:K05044]
123777639  SLC6A12; sodium- and chloride-dependent betaine transporter [KO:K05045]
123801396  GLUL; glutamine synthetase isoform X1 [KO:K01915] [EC:6.3.1.2]
123798682  SLC38A3; sodium-coupled neutral amino acid transporter 3 isoform X1 [KO:K13576]
123787949  SLC38A5; LOW QUALITY PROTEIN: sodium-coupled neutral amino acid transporter 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
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
uar00020  Citrate cycle (TCA cycle)
uar00250  Alanine, aspartate and glutamate metabolism
uar04144  Endocytosis
uar04721  Synaptic vesicle cycle
KO pathway
ko04727   
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