KEGG   PATHWAY: rno04727
Entry
rno04727                    Pathway                                
Name
GABAergic synapse - Rattus norvegicus (rat)
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
rno04727  GABAergic synapse
rno04727

Other DBs
GO: 0051932
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
114117  Gng3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
114118  Gng4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
114119  Gng10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
114120  Gng12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
114493  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
120098596  Gabarapl4; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
134484162  [KO:K08341]
140674  Gabrg1; gamma-aminobutyric acid receptor subunit gamma-1 precursor [KO:K05186]
140675  Gabra4; gamma-aminobutyric acid receptor subunit alpha-4 precursor [KO:K05175]
170567  Slc38a1; sodium-coupled neutral amino acid symporter 1 [KO:K14990]
171086  Trak2; trafficking kinesin-binding protein 2 [KO:K15374]
171163  Slc6a13; sodium- and chloride-dependent GABA transporter 2 [KO:K05046]
171373  Slc12a5; solute carrier family 12 member 5 isoform 2 [KO:K23967]
192208  Slc38a5; sodium-coupled neutral amino acid transporter 5 [KO:K14992]
192258  Gabrr3; gamma-aminobutyric acid receptor subunit rho-3 precursor [KO:K05190]
192268  Gls2; glutaminase liver isoform, mitochondrial isoform 1 [KO:K01425] [EC:3.5.1.2]
24239  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
24379  Gad1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
24380  Gad2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
24398  Gls; glutaminase kidney isoform, mitochondrial isoform a [KO:K01425] [EC:3.5.1.2]
24400  Gnb1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
245986  Gng8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
24681  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
24922  Gabrb3; gamma-aminobutyric acid receptor subunit beta-3 precursor [KO:K05181]
24947  Gabra3; gamma-aminobutyric acid receptor subunit alpha-3 precursor [KO:K05175]
24957  Glul; glutamine synthetase [KO:K01915] [EC:6.3.1.2]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:4.6.1.1]
252919  Slc38a3; sodium-coupled neutral amino acid transporter 3 [KO:K13576]
25398  Cacna1a; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
25450  Gabrb1; gamma-aminobutyric acid receptor subunit beta-1 precursor [KO:K05181]
25451  Gabrb2; gamma-aminobutyric acid receptor subunit beta-2 precursor [KO:K05181]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
25643  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
25686  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
25743  Kcnj6; G protein-activated inward rectifier potassium channel 2 isoform 1 [KO:K05000]
257648  Cacna1b; voltage-dependent N-type calcium channel subunit alpha-1B isoform 1 [KO:K04849]
289606  Gabra2; gamma-aminobutyric acid receptor subunit alpha-2 precursor [KO:K05175]
29241  Adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
29430  Hap1; huntingtin-associated protein 1 isoform B [KO:K04647]
294962  Gnb4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
29642  Slc38a2; sodium-coupled neutral amino acid symporter 2 [KO:K14207]
29689  Gabrd; gamma-aminobutyric acid receptor subunit delta precursor [KO:K05184]
29694  Gabrr1; gamma-aminobutyric acid receptor subunit rho-1 precursor [KO:K05190]
29695  Gabrr2; gamma-aminobutyric acid receptor subunit rho-2 precursor [KO:K05190]
29705  Gabra1; gamma-aminobutyric acid receptor subunit alpha-1 precursor [KO:K05175]
29707  Gabra5; gamma-aminobutyric acid receptor subunit alpha-5 precursor [KO:K05175]
29708  Gabra6; gamma-aminobutyric acid receptor subunit alpha-6 precursor [KO:K05175]
29709  Gabrg2; gamma-aminobutyric acid receptor subunit gamma-2 isoform 2 precursor [KO:K05186]
29716  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
302950  Adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
305509  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
50664  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha isoform B [KO:K04534]
50676  Slc6a12; sodium- and chloride-dependent betaine transporter [KO:K05045]
54223  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
58974  Gabarap; gamma-aminobutyric acid receptor-associated protein [KO:K08341]
58979  Gng7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
60355  Nsf; vesicle-fusing ATPase [KO:K06027] [EC:3.6.4.6]
60449  Gnb3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
64199  Gng11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
64508  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
64670  Gabarapl2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
64845  Gphn; gephyrin [KO:K15376] [EC:2.10.1.1 2.7.7.75]
65187  Gabrq; gamma-aminobutyric acid receptor subunit theta precursor [KO:K05192]
65191  Gabre; gamma-aminobutyric acid receptor subunit epsilon precursor [KO:K05185]
680149  Gngt1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
682930  Cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
685451  Gng13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
685513  Gng14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
689161  Gabarapl1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
690825  Gngt2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
79211  Gabrg3; gamma-aminobutyric acid receptor subunit gamma-3 precursor [KO:K05186]
79212  Slc6a1; sodium- and chloride-dependent GABA transporter 1 [KO:K05034]
79213  Slc6a11; sodium- and chloride-dependent GABA transporter 3 [KO:K05044]
79218  Gng5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
80850  Gng2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
81632  Abat; 4-aminobutyrate aminotransferase, mitochondrial [KO:K13524] [EC:2.6.1.19 2.6.1.22]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
81657  Gabbr1; gamma-aminobutyric acid type B receptor subunit 1 precursor [KO:K04615]
81658  Gabrp; gamma-aminobutyric acid receptor subunit pi precursor [KO:K05189]
81664  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
81667  Gnb2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
83579  Gnb5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
83612  Slc32a1; vesicular inhibitory amino acid transporter [KO:K15015]
83633  Gabbr2; gamma-aminobutyric acid type B receptor subunit 2 precursor [KO:K04615]
83805  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
84420  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
84587  Plcl1; inactive phospholipase C-like protein 1 [KO:K15375]
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
rno00020  Citrate cycle (TCA cycle)
rno00250  Alanine, aspartate and glutamate metabolism
rno04144  Endocytosis
rno04721  Synaptic vesicle cycle
KO pathway
ko04727   

DBGET integrated database retrieval system