KEGG   PATHWAY: ptr04727
Entry
ptr04727                    Pathway                                
Name
GABAergic synapse - Pan troglodytes (chimpanzee)
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
ptr04727  GABAergic synapse
ptr04727

Other DBs
GO: 0051932
Organism
Pan troglodytes (chimpanzee) [GN:ptr]
Gene
100608010  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
100609242  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 isoform X1 [KO:K04347]
100611518  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
100612078  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
100614945  SLC6A13; sodium- and chloride-dependent GABA transporter 2 isoform X2 [KO:K05046]
107966260  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
107966421  GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192]
107968762  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
107968982  NSF; vesicle-fusing ATPase isoform X1 [KO:K06027] [EC:3.6.4.6]
107969673  GNG14; LOW QUALITY PROTEIN: putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
107969769  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 isoform X2 [KO:K04544]
107971226  GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185]
129135276  TRAK2; trafficking kinesin-binding protein 2 isoform X1 [KO:K15374]
129136331  [KO:K04542]
129137227  [KO:K04545]
450173  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X2 [KO:K04534]
451850  SLC38A1; sodium-coupled neutral amino acid symporter 1 isoform X1 [KO:K14990]
451851  SLC38A2; sodium-coupled neutral amino acid symporter 2 isoform X1 [KO:K14207]
451866  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
451998  GLS2; glutaminase liver isoform, mitochondrial isoform X2 [KO:K01425] [EC:3.5.1.2]
452819  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
452976  GPHN; gephyrin isoform X22 [KO:K15376] [EC:2.10.1.1 2.7.7.75]
453265  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 isoform X1 [KO:K05181]
453869  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
453993  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
454251  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
454832  PRKCA; protein kinase C alpha type isoform X2 [KO:K02677] [EC:2.7.11.13]
455766  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X3 [KO:K04344]
456276  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
456450  GLUL; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
456977  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
457093  GNAI3; guanine nucleotide-binding protein G(I) subunit alpha-3 [KO:K04630]
458229  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
458295  SLC12A5; solute carrier family 12 member 5 isoform X1 [KO:K23967]
459070  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
460169  SLC6A11; sodium- and chloride-dependent GABA transporter 3 [KO:K05044]
460170  SLC6A1; sodium- and chloride-dependent GABA transporter 1 [KO:K05034]
460447  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X20 [KO:K04851]
460862  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
461352  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 isoform X1 [KO:K05181]
461355  GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 isoform X1 [KO:K05175]
462240  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181]
462241  GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175]
462242  GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186]
463392  ADCY1; adenylate cyclase type 1 isoform X2 [KO:K08041] [EC:4.6.1.1]
464400  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
464609  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
464893  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B isoform X1 [KO:K04849]
465914  GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 [KO:K05175]
466026  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
466915  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
467192  SLC6A12; sodium- and chloride-dependent betaine transporter isoform X1 [KO:K05045]
467457  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
467624  GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 isoform X1 [KO:K05186]
467760  [KO:K08341]
468557  GAD1; glutamate decarboxylase 1 isoform X1 [KO:K01580] [EC:4.1.1.15]
469367  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X6 [KO:K04345] [EC:2.7.11.11]
469458  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
469635  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
469940  SLC32A1; vesicular inhibitory amino acid transporter [KO:K15015]
470606  GLS; glutaminase kidney isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
470611  PLCL1; inactive phospholipase C-like protein 1 isoform X1 [KO:K15375]
470869  GABRR3; gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190]
470905  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
471392  GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 isoform X2 [KO:K05175]
471725  GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175]
471736  GABRP; gamma-aminobutyric acid receptor subunit PI [KO:K05189]
471946  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X4 [KO:K04615]
472068  GABRR1; gamma-aminobutyric acid receptor subunit rho-1 isoform X1 [KO:K05190]
472069  GABRR2; gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190]
472425  GNAI1; guanine nucleotide-binding protein G(I) subunit alpha-1 isoform X1 [KO:K04630]
472944  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
473278  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
473596  SLC38A5; sodium-coupled neutral amino acid transporter 5 isoform X1 [KO:K14992]
474111  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
737951  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 isoform X2 [KO:K08341]
739897  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
740711  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
740869  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
743331  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
743382  HAP1; huntingtin-associated protein 1 isoform X4 [KO:K04647]
744391  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
744706  SLC38A3; sodium-coupled neutral amino acid transporter 3 [KO:K13576]
744773  GNAI2; guanine nucleotide-binding protein G(I) subunit alpha-2 [KO:K04630]
744855  GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175]
745402  GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
747170  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
747185  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
747186  GABRD; gamma-aminobutyric acid receptor subunit delta isoform X1 [KO:K05184]
748888  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
749133  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
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
ptr00020  Citrate cycle (TCA cycle)
ptr00250  Alanine, aspartate and glutamate metabolism
ptr04144  Endocytosis
ptr04721  Synaptic vesicle cycle
KO pathway
ko04727   

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