KEGG   PATHWAY: pcad04727
Entry
pcad04727                   Pathway                                
Name
GABAergic synapse - Physeter catodon (sperm 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
pcad04727  GABAergic synapse
pcad04727

Other DBs
GO: 0051932
Organism
Physeter catodon (sperm whale) [GN:pcad]
Gene
102983261  SLC38A1; sodium-coupled neutral amino acid symporter 1 isoform X1 [KO:K14990]
102982789  SLC38A2; sodium-coupled neutral amino acid symporter 2 isoform X2 [KO:K14207]
102984477  GLS2; glutaminase liver isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
102978503  GLS; glutaminase kidney isoform, mitochondrial isoform X4 [KO:K01425] [EC:3.5.1.2]
102995985  GAD1; glutamate decarboxylase 1 isoform X1 [KO:K01580] [EC:4.1.1.15]
102988357  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
102995853  SLC32A1; vesicular inhibitory amino acid transporter [KO:K15015]
102995298  ABAT; 4-aminobutyrate aminotransferase, mitochondrial [KO:K13524] [EC:2.6.1.19 2.6.1.22]
102991125  GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 [KO:K05175]
102996489  GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175]
102994126  GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175]
102984190  GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 isoform X1 [KO:K05175]
102992339  GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175]
102973669  GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 isoform X1 [KO:K05175]
102983355  LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit alpha-5-like [KO:K05175]
102996682  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181]
102980778  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 isoform X1 [KO:K05181]
102973484  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 [KO:K05181]
102986773  GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186]
102976176  GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 [KO:K05186]
102992547  GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186]
102988911  GABRD; gamma-aminobutyric acid receptor subunit delta isoform X1 [KO:K05184]
102979985  GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185]
102978804  GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192]
102985185  GABRP; gamma-aminobutyric acid receptor subunit pi [KO:K05189]
102981091  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102995361  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
102983882  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
102974888  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
102974383  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
102983841  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
102995463  HAP1; huntingtin-associated protein 1 [KO:K04647]
102996693  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
102994264  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 isoform X1 [KO:K08341]
102973481  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 isoform X1 [KO:K08341]
102993946  NSF; vesicle-fusing ATPase isoform X1 [KO:K06027] [EC:3.6.4.6]
102987419  TRAK2; trafficking kinesin-binding protein 2 isoform X1 [KO:K15374]
102986490  PLCL1; inactive phospholipase C-like protein 1 [KO:K15375]
102995217  GPHN; gephyrin isoform X5 [KO:K15376] [EC:2.10.1.1 2.7.7.75]
102978221  SLC12A5; solute carrier family 12 member 5 isoform X1 [KO:K23967]
102993642  GABRR2; gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190]
102993925  GABRR1; gamma-aminobutyric acid receptor subunit rho-1 [KO:K05190]
102979171  GABRR3; LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190]
102977865  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
102983972  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849]
102989784  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
102976068  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
102992313  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
102987099  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X10 [KO:K04857]
102993343  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X3 [KO:K04615]
102975766  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
102996618  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
102997009  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
102996666  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
102986172  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
102975750  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
102982318  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
102990164  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
102995518  GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539]
102981323  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 isoform X2 [KO:K07826]
102975548  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
102976421  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
112063837  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
112062012  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542]
112064782  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542]
112067655  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
112067178  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
102985729  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
102994418  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
112063854  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
102976485  GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
112066479  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
112066563  GNGT2; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
102981199  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
102991224  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
102989136  ADCY3; adenylate cyclase type 3 isoform X3 [KO:K08043] [EC:4.6.1.1]
102985820  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
102983319  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
102986152  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
102985075  ADCY7; adenylate cyclase type 7 isoform X4 [KO:K08047] [EC:4.6.1.1]
102975211  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
102995803  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
102995845  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
102985268  SLC6A1; sodium- and chloride-dependent GABA transporter 1 [KO:K05034]
102993609  SLC6A13; sodium- and chloride-dependent GABA transporter 2 isoform X1 [KO:K05046]
102985838  SLC6A11; sodium- and chloride-dependent GABA transporter 3 [KO:K05044]
102988646  SLC6A12; sodium- and chloride-dependent betaine transporter [KO:K05045]
102989047  GLUL; glutamine synthetase isoform X1 [KO:K01915] [EC:6.3.1.2]
102996335  SLC38A3; sodium-coupled neutral amino acid transporter 3 isoform X2 [KO:K13576]
102993154  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
pcad00020  Citrate cycle (TCA cycle)
pcad00250  Alanine, aspartate and glutamate metabolism
pcad04144  Endocytosis
pcad04721  Synaptic vesicle cycle
KO pathway
ko04727   
LinkDB

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