KEGG   PATHWAY: elk04727
Entry
elk04727                    Pathway                                
Name
GABAergic synapse - Enhydra lutris kenyoni (northern sea otter)
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
elk04727  GABAergic synapse
elk04727

Other DBs
GO: 0051932
Organism
Enhydra lutris kenyoni (northern sea otter) [GN:elk]
Gene
111158010  sodium-coupled neutral amino acid transporter 1 [KO:K14990]
111157806  sodium-coupled neutral amino acid transporter 2 isoform X1 [KO:K14207]
111142001  glutaminase kidney isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
111160161  glutaminase liver isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
111154283  LOW QUALITY PROTEIN: glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
111139699  glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
111149803  glutamate decarboxylase 1 isoform X1 [KO:K01580] [EC:4.1.1.15]
111141928  vesicular inhibitory amino acid transporter [KO:K15015]
111156046  4-aminobutyrate aminotransferase, mitochondrial [KO:K13524] [EC:2.6.1.19 2.6.1.22]
111161924  gamma-aminobutyric acid receptor subunit alpha-5 [KO:K05175]
111149113  gamma-aminobutyric acid receptor subunit alpha-2 [KO:K05175]
111149120  gamma-aminobutyric acid receptor subunit alpha-4 isoform X1 [KO:K05175]
111139171  gamma-aminobutyric acid receptor subunit alpha-3 [KO:K05175]
111141067  gamma-aminobutyric acid receptor subunit alpha-1 [KO:K05175]
111141113  gamma-aminobutyric acid receptor subunit alpha-6 [KO:K05175]
111149058  gamma-aminobutyric acid receptor subunit beta-1 isoform X1 [KO:K05181]
111141129  LOW QUALITY PROTEIN: gamma-aminobutyric acid receptor subunit beta-2 [KO:K05181]
111161915  gamma-aminobutyric acid receptor subunit beta-3 isoform X1 [KO:K05181]
111161925  gamma-aminobutyric acid receptor subunit gamma-3 [KO:K05186]
111141021  gamma-aminobutyric acid receptor subunit gamma-2 isoform X1 [KO:K05186]
111149188  gamma-aminobutyric acid receptor subunit gamma-1 [KO:K05186]
111154882  gamma-aminobutyric acid receptor subunit delta [KO:K05184]
111139198  gamma-aminobutyric acid receptor subunit epsilon [KO:K05185]
111139218  gamma-aminobutyric acid receptor subunit theta [KO:K05192]
111141225  gamma-aminobutyric acid receptor subunit pi isoform X1 [KO:K05189]
111162516  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
111143399  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
111141563  proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
111158087  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
111162208  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
111139613  protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
111151488  LOW QUALITY PROTEIN: huntingtin-associated protein 1 [KO:K04647]
111152932  gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
111161123  gamma-aminobutyric acid receptor-associated protein isoform X1 [KO:K08341]
111142199  gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
111158089  vesicle-fusing ATPase [KO:K06027] [EC:3.6.4.6]
111145012  trafficking kinesin-binding protein 2 [KO:K15374]
111141861  inactive phospholipase C-like protein 1 [KO:K15375]
111148720  gephyrin [KO:K15376] [EC:2.10.1.1 2.7.7.75]
111141395  solute carrier family 12 member 5 isoform X1 [KO:K23967]
111158815  gamma-aminobutyric acid receptor subunit rho-2 [KO:K05190]
111158823  gamma-aminobutyric acid receptor subunit rho-1 isoform X1 [KO:K05190]
111151629  gamma-aminobutyric acid receptor subunit rho-3 [KO:K05190]
111162543  voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X1 [KO:K04344]
111145672  voltage-dependent N-type calcium channel subunit alpha-1B isoform X1 [KO:K04849]
111159674  voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
111143738  voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
111150407  voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
111150995  voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
111145857  gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
111162572  gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
111155312  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
111143783  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
111143343  guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
111157367  guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
111154601  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
111145586  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 isoform X1 [KO:K04537]
111159773  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
111148588  guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
111140421  guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
111159618  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 isoform X1 [KO:K07826]
111149566  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
111160502  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
111143000  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
111161718  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
111160835  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
111145828  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
111147333  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
111162432  uncharacterized LOC105372280 homolog [KO:K04347]
111142967  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
111156207  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
111147281  guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
111151818  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
111157054  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
111153427  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
111154044  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
111162403  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
111155044  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
111157825  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
111157326  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
111146667  adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
111156133  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
111155756  G protein-activated inward rectifier potassium channel 2 [KO:K05000]
111144145  sodium- and chloride-dependent GABA transporter 1 [KO:K05034]
111159726  sodium- and chloride-dependent GABA transporter 2 [KO:K05046]
111144092  sodium- and chloride-dependent GABA transporter 3 [KO:K05044]
111159720  sodium- and chloride-dependent betaine transporter isoform X1 [KO:K05045]
111150722  glutamine synthetase isoform X1 [KO:K01915] [EC:6.3.1.2]
111144143  sodium-coupled neutral amino acid transporter 3 isoform X1 [KO:K13576]
111150496  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
elk00020  Citrate cycle (TCA cycle)
elk00250  Alanine, aspartate and glutamate metabolism
elk04144  Endocytosis
elk04721  Synaptic vesicle cycle
KO pathway
ko04727   
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