KEGG   PATHWAY: hmh04727
Entry
hmh04727                    Pathway                                
Name
GABAergic synapse - Hylobates moloch (silvery gibbon)
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
hmh04727  GABAergic synapse
hmh04727

Other DBs
GO: 0051932
Organism
Hylobates moloch (silvery gibbon) [GN:hmh]
Gene
116481102  SLC38A1; sodium-coupled neutral amino acid symporter 1 isoform X1 [KO:K14990]
116481103  SLC38A2; sodium-coupled neutral amino acid symporter 2 isoform X1 [KO:K14207]
116810531  GLS; glutaminase kidney isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
116480904  GLS2; glutaminase liver isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
116810675  GAD1; glutamate decarboxylase 1 isoform X1 [KO:K01580] [EC:4.1.1.15]
116462434  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
116461130  SLC32A1; vesicular inhibitory amino acid transporter [KO:K15015]
116462289  ABAT; 4-aminobutyrate aminotransferase, mitochondrial [KO:K13524] [EC:2.6.1.19 2.6.1.22]
116471803  GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175]
116471804  GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 isoform X1 [KO:K05175]
116812098  GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 isoform X1 [KO:K05175]
116482068  GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175]
116456644  GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 isoform X1 [KO:K05175]
116456671  GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 [KO:K05175]
116471802  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181]
116482332  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 isoform X1 [KO:K05181]
116456670  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 isoform X1 [KO:K05181]
116471806  GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X3 [KO:K05186]
116482650  GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 isoform X1 [KO:K05186]
116456849  GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 [KO:K05186]
116812798  GABRD; gamma-aminobutyric acid receptor subunit delta [KO:K05184]
116812103  GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185]
116812099  GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192]
116471841  GABRP; gamma-aminobutyric acid receptor subunit pi isoform X1 [KO:K05189]
116458418  PRKACG; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
116469844  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116478588  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
116461023  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
116483969  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
116471147  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
116479165  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
116474837  HAP1; LOW QUALITY PROTEIN: huntingtin-associated protein 1 [KO:K04647]
116459322  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
116470809  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
116463324  gamma-aminobutyric acid receptor-associated protein-like 3 [KO:K08341]
116472669  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
116463648  gamma-aminobutyric acid receptor-associated protein-like 3 [KO:K08341]
116474994  NSF; vesicle-fusing ATPase isoform X1 [KO:K06027] [EC:3.6.4.6]
116810452  TRAK2; trafficking kinesin-binding protein 2 [KO:K15374]
116810491  PLCL1; inactive phospholipase C-like protein 1 isoform X1 [KO:K15375]
116484482  GPHN; gephyrin isoform X1 [KO:K15376] [EC:2.10.1.1 2.7.7.75]
116461333  SLC12A5; solute carrier family 12 member 5 isoform X2 [KO:K23967]
116469682  GABRR1; gamma-aminobutyric acid receptor subunit rho-1 isoform X1 [KO:K05190]
116469699  GABRR2; gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190]
116466351  GABRR3; gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190]
116478572  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X2 [KO:K04344]
116475947  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B isoform X1 [KO:K04849]
116472525  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
116473372  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X9 [KO:K04851]
116811686  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
116457338  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
116460519  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
116475316  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 isoform X1 [KO:K04615]
116469652  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
116464223  guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
116464225  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
116814165  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
116471265  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
116812793  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
116463853  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 isoform X1 [KO:K04537]
116463857  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 isoform X1 [KO:K04537]
116472600  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
116481481  GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
116484566  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 isoform X3 [KO:K07826]
116468899  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
116457634  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
116476763  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
116457866  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542]
116469841  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
116811956  GNG5B; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5B [KO:K04542]
116477213  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542]
116483152  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
116478306  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 isoform X1 [KO:K04544]
116475542  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
116814102  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
116469917  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
116462301  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
116814103  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
116474673  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
116812469  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
116457100  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
116480405  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
116484980  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
116466852  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
116461805  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
116471246  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
116813595  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
116462297  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
116481525  KCNJ6; G protein-activated inward rectifier potassium channel 2 isoform X1 [KO:K05000]
116466739  SLC6A1; sodium- and chloride-dependent GABA transporter 1 [KO:K05034]
116472500  SLC6A13; sodium- and chloride-dependent GABA transporter 2 isoform X1 [KO:K05046]
116466738  SLC6A11; sodium- and chloride-dependent GABA transporter 3 [KO:K05044]
116472501  SLC6A12; sodium- and chloride-dependent betaine transporter [KO:K05045]
116458010  GLUL; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
116473465  SLC38A3; sodium-coupled neutral amino acid transporter 3 [KO:K13576]
116811654  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
hmh00020  Citrate cycle (TCA cycle)
hmh00250  Alanine, aspartate and glutamate metabolism
hmh04144  Endocytosis
hmh04721  Synaptic vesicle cycle
KO pathway
ko04727   
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