KEGG   PATHWAY: lav04727
Entry
lav04727                    Pathway                                
Name
GABAergic synapse - Loxodonta africana (African savanna elephant)
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
lav04727  GABAergic synapse
lav04727

Other DBs
GO: 0051932
Organism
Loxodonta africana (African savanna elephant) [GN:lav]
Gene
100672492  SLC38A1; sodium-coupled neutral amino acid transporter 1 isoform X1 [KO:K14990]
100672778  SLC38A2; sodium-coupled neutral amino acid transporter 2 isoform X1 [KO:K14207]
100668982  GLS; glutaminase kidney isoform, mitochondrial isoform X4 [KO:K01425] [EC:3.5.1.2]
100673149  GLS2; glutaminase liver isoform, mitochondrial [KO:K01425] [EC:3.5.1.2]
100666234  GAD1; glutamate decarboxylase 1 isoform X1 [KO:K01580] [EC:4.1.1.15]
100667678  GAD2; LOW QUALITY PROTEIN: glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
100662733  glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
100653936  SLC32A1; LOW QUALITY PROTEIN: vesicular inhibitory amino acid transporter [KO:K15015]
100666671  ABAT; 4-aminobutyrate aminotransferase, mitochondrial [KO:K13524] [EC:2.6.1.19 2.6.1.22]
100659390  GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175]
100659678  GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175]
100673112  GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 isoform X1 [KO:K05175]
100665743  GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 [KO:K05175]
100662419  GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175]
100666647  GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 [KO:K05175]
100658920  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181]
100673796  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 isoform X1 [KO:K05181]
100662142  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 isoform X1 [KO:K05181]
100659961  GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186]
100666363  GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 [KO:K05186]
100662697  GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186]
100676800  GABRD; gamma-aminobutyric acid receptor subunit delta [KO:K05184]
100670286  GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185]
100666025  GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192]
100663560  GABRP; gamma-aminobutyric acid receptor subunit pi [KO:K05189]
100656966  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100674245  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100675475  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
100665537  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
100672078  PRKCB; LOW QUALITY PROTEIN: protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
100671733  PRKCG; LOW QUALITY PROTEIN: protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100669585  HAP1; huntingtin-associated protein 1 isoform X3 [KO:K04647]
100659994  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
100675686  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
100658035  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
100659266  NSF; vesicle-fusing ATPase [KO:K06027] [EC:3.6.4.6]
100660257  TRAK2; LOW QUALITY PROTEIN: trafficking kinesin-binding protein 2 [KO:K15374]
100666710  PLCL1; LOW QUALITY PROTEIN: inactive phospholipase C-like protein 1 [KO:K15375]
100662938  GPHN; gephyrin [KO:K15376] [EC:2.10.1.1 2.7.7.75]
100665891  SLC12A5; LOW QUALITY PROTEIN: solute carrier family 12 member 5 [KO:K23967]
100670099  GABRR2; gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190]
100670389  GABRR1; gamma-aminobutyric acid receptor subunit rho-1 isoform X2 [KO:K05190]
100665222  GABRR3; LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190]
100655176  CACNA1A; LOW QUALITY PROTEIN: voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
100660444  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849]
100659992  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
100674649  CACNA1F; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
100673089  CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
100657108  GABBR1; LOW QUALITY PROTEIN: gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
100657997  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
100666344  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
100670234  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100667957  GNAI3; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
100658419  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
100673391  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
100677127  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
100674807  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
100669106  GNB4; LOW QUALITY PROTEIN: guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
100674665  GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539]
100668996  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 isoform X2 [KO:K07826]
100676083  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
100664179  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
100656403  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
100655407  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
100662559  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
111749727  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
111751488  GNG14; LOW QUALITY PROTEIN: putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
111750996  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
100675882  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
111749728  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
111751775  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
100671072  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100673570  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100674724  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
100675525  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
100670244  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100653532  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
100653771  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100661616  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
100663448  ADCY9; LOW QUALITY PROTEIN: adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
100676455  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
100657816  SLC6A1; sodium- and chloride-dependent GABA transporter 1 [KO:K05034]
111750861  SLC6A13; sodium- and chloride-dependent GABA transporter 2 isoform X1 [KO:K05046]
100658105  SLC6A11; LOW QUALITY PROTEIN: sodium- and chloride-dependent GABA transporter 3 [KO:K05044]
100666456  sodium- and chloride-dependent betaine transporter [KO:K05045]
100673871  GLUL; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
100670517  SLC38A3; sodium-coupled neutral amino acid transporter 3 isoform X1 [KO:K13576]
100654913  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
lav00020  Citrate cycle (TCA cycle)
lav00250  Alanine, aspartate and glutamate metabolism
lav04144  Endocytosis
lav04721  Synaptic vesicle cycle
KO pathway
ko04727   
LinkDB

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