KEGG   PATHWAY: lww04727
Entry
lww04727                    Pathway                                
Name
GABAergic synapse - Leptonychotes weddellii (Weddell seal)
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
lww04727  GABAergic synapse
lww04727

Other DBs
GO: 0051932
Organism
Leptonychotes weddellii (Weddell seal) [GN:lww]
Gene
102739006  SLC38A1; sodium-coupled neutral amino acid transporter 1 [KO:K14990]
102739304  SLC38A2; sodium-coupled neutral amino acid transporter 2 isoform X1 [KO:K14207]
102741300  GLS2; glutaminase liver isoform, mitochondrial [KO:K01425] [EC:3.5.1.2]
102731303  GLS; glutaminase kidney isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
102731758  glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
102726082  GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
102730178  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
102731182  SLC32A1; vesicular inhibitory amino acid transporter [KO:K15015]
102734230  ABAT; 4-aminobutyrate aminotransferase, mitochondrial [KO:K13524] [EC:2.6.1.19 2.6.1.22]
102738755  GABRA6; gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175]
102739064  GABRA1; gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175]
102740524  GABRA2; gamma-aminobutyric acid receptor subunit alpha-2 isoform X2 [KO:K05175]
102740822  GABRA4; gamma-aminobutyric acid receptor subunit alpha-4 [KO:K05175]
102748911  GABRA5; gamma-aminobutyric acid receptor subunit alpha-5 isoform X1 [KO:K05175]
102742499  GABRA3; gamma-aminobutyric acid receptor subunit alpha-3 [KO:K05175]
102740651  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 [KO:K05181]
102734981  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 [KO:K05181]
102748008  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 [KO:K05181]
102739560  GABRG2; gamma-aminobutyric acid receptor subunit gamma-2 isoform X2 [KO:K05186]
102730832  GABRG3; gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186]
102740027  GABRG1; gamma-aminobutyric acid receptor subunit gamma-1 isoform X1 [KO:K05186]
102729118  GABRD; gamma-aminobutyric acid receptor subunit delta isoform X3 [KO:K05184]
102741886  GABRE; gamma-aminobutyric acid receptor subunit epsilon [KO:K05185]
102733644  GABRQ; gamma-aminobutyric acid receptor subunit theta [KO:K05192]
102748358  GABRP; gamma-aminobutyric acid receptor subunit pi isoform X1 [KO:K05189]
102735449  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
102729236  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102734775  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:2.7.10.2]
102732903  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
102741890  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
102748284  HAP1; huntingtin-associated protein 1 isoform X1 [KO:K04647]
102734169  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
102741567  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
102735874  GABARAP; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
102732734  trafficking kinesin-binding protein 2 [KO:K15374]
102729889  PLCL1; inactive phospholipase C-like protein 1 [KO:K15375]
102739689  GPHN; gephyrin [KO:K15376] [EC:2.10.1.1 2.7.7.75]
102726643  solute carrier family 12 member 5 [KO:K23967]
102731051  GABRR1; gamma-aminobutyric acid receptor subunit rho-1 [KO:K05190]
102731367  gamma-aminobutyric acid receptor subunit rho-2 isoform X1 [KO:K05190]
102746762  GABRR3; LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190]
102731073  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
102742095  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
102745809  CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
102743554  gamma-aminobutyric acid type B receptor subunit 1-like [KO:K04615]
102741826  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
102749728  gamma-aminobutyric acid type B receptor subunit 1 [KO:K04615]
102750373  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
102726697  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
102749575  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
102737331  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
102733062  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
102745475  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
102740677  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
102732783  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 isoform X1 [KO:K07825]
102733448  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
102725604  GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
102725746  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
102744808  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
102747228  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
102748197  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
102732481  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
102735164  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
102749236  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
102731100  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
102729125  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
102742669  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
102748147  GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
102736718  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
102739395  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 isoform X2 [KO:K04547]
102743177  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
102735798  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 isoform X2 [KO:K04549]
102739347  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
102741598  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
102729355  adenylate cyclase type 4-like isoform X1 [KO:K08044] [EC:4.6.1.1]
102750941  adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
102734024  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
102732736  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
102733005  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
102728665  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
102733832  KCNJ6; G protein-activated inward rectifier potassium channel 2 [KO:K05000]
102751066  SLC6A1; sodium- and chloride-dependent GABA transporter 1 [KO:K05034]
115945017  SLC6A13; sodium- and chloride-dependent GABA transporter 2 [KO:K05046]
102725638  sodium- and chloride-dependent GABA transporter 3 [KO:K05044]
102742720  SLC6A12; sodium- and chloride-dependent betaine transporter isoform X1 [KO:K05045]
102747244  GLUL; glutamine synthetase isoform X1 [KO:K01915] [EC:6.3.1.2]
102727012  SLC38A3; sodium-coupled neutral amino acid transporter 3 isoform X1 [KO:K13576]
102729954  SLC38A5; 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
lww00020  Citrate cycle (TCA cycle)
lww00250  Alanine, aspartate and glutamate metabolism
lww04144  Endocytosis
lww04721  Synaptic vesicle cycle
KO pathway
ko04727   
LinkDB

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