KEGG   PATHWAY: pcw04726
Entry
pcw04726                    Pathway                                
Name
Serotonergic synapse - Phascolarctos cinereus (koala)
Description
Serotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter that plays important roles in physiological functions such as learning and memory, emotion, sleep, pain, motor function and endocrine secretion, as well as in pathological states including abnormal mood and cognition. Once released from presynaptic axonal terminals, 5-HT binds to receptors, which have been divided into 7 subfamilies on the basis of conserved structures and signaling mechanisms. These families include the ionotropic 5-HT3 receptors and G-protein-coupled 5-HT receptors, the 5-HT1 (Gi /Go -coupled), 5-HT2(Gq-coupled), 5-HT4/6/7 (Gs-coupled) and 5-HT5 receptors. Presynaptically localized 5-HT1B receptors are thought to be the autoreceptors that suppress excess 5-HT release. 5-HT's actions are terminated by transporter- mediated reuptake into neurons, leading to catabolism by monoamine oxidase.
Class
Organismal Systems; Nervous system
Pathway map
pcw04726  Serotonergic synapse
pcw04726

Other DBs
GO: 0007210
Organism
Phascolarctos cinereus (koala) [GN:pcw]
Gene
110221097  TPH1; LOW QUALITY PROTEIN: tryptophan 5-hydroxylase 1 [KO:K00502] [EC:1.14.16.4]
110195961  TPH2; LOW QUALITY PROTEIN: tryptophan 5-hydroxylase 2 [KO:K00502] [EC:1.14.16.4]
110205002  DDC; aromatic-L-amino-acid decarboxylase [KO:K01593] [EC:4.1.1.28 4.1.1.105]
110209553  SLC18A2; synaptic vesicular amine transporter isoform X1 [KO:K08155]
110196419  SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155]
110218748  CACNA1C; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
110197022  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
110201034  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
110219570  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
110213438  HTR2A; 5-hydroxytryptamine receptor 2A [KO:K04157]
110192373  HTR2C; 5-hydroxytryptamine receptor 2C isoform X1 [KO:K04157]
110198031  HTR2B; 5-hydroxytryptamine receptor 2B isoform X1 [KO:K04157]
110214560  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
110195440  PLCB3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
110223673  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
110207938  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
110207974  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
110195613  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
110193334  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
110217180  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
110218307  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
110214622  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
110220182  PRKCG; LOW QUALITY PROTEIN: protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
110221918  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110215167  MAPK1; LOW QUALITY PROTEIN: mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
110219868  PLA2G4C; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
110223640  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
110223689  LOW QUALITY PROTEIN: cytosolic phospholipase A2 beta-like [KO:K16342] [EC:3.1.1.4]
110223735  PLA2G4F; LOW QUALITY PROTEIN: cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
110223736  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
110206877  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
110200601  cytochrome P450 2C23-like [KO:K07413] [EC:1.14.14.1]
110215468  cytochrome P450 2C19-like isoform X1 [KO:K07413] [EC:1.14.14.1]
110200600  cytochrome P450 2C23-like isoform X1 [KO:K07413] [EC:1.14.14.1]
110213986  cytochrome P450 2C23-like [KO:K07413] [EC:1.14.14.1]
110192769  cytochrome P450 2C19-like isoform X1 [KO:K07413] [EC:1.14.14.1]
110205862  cytochrome P450 2D14 [KO:K07414] [EC:1.14.14.1]
110212934  cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
110212942  cytochrome P450 2J2-like isoform X1 [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
110212976  cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
110212978  LOW QUALITY PROTEIN: cytochrome P450 2J2-like [KO:K07418] [EC:1.14.14.1 1.14.14.73 1.14.14.74 1.14.14.75]
110209311  cytochrome P450 4X1-like isoform X1 [KO:K07428] [EC:1.14.14.1]
110213916  ALOX5; arachidonate 5-lipoxygenase [KO:K00461] [EC:1.13.11.34]
110194257  arachidonate 12-lipoxygenase, 12S-type-like isoform X1 [KO:K00458] [EC:1.13.11.31]
110194205  ALOX12B; arachidonate 12-lipoxygenase, 12R-type [KO:K08021] [EC:1.13.11.-]
110194258  LOW QUALITY PROTEIN: arachidonate 15-lipoxygenase-like [KO:K00460] [EC:1.13.11.33]
110194982  prostaglandin G/H synthase 1-like [KO:K00509] [EC:1.14.99.1]
110194994  prostaglandin G/H synthase 1-like [KO:K00509] [EC:1.14.99.1]
110206875  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
110221181  LOW QUALITY PROTEIN: 5-hydroxytryptamine receptor 3E-like [KO:K04819]
110221335  5-hydroxytryptamine receptor 3C-like [KO:K04819]
110210755  HTR3A; 5-hydroxytryptamine receptor 3A [KO:K04819]
110210766  HTR3B; 5-hydroxytryptamine receptor 3B [KO:K04819]
110196048  HTR4; 5-hydroxytryptamine receptor 4 isoform X1 [KO:K04160]
110198745  HTR6; 5-hydroxytryptamine receptor 6 [KO:K04162]
110192789  HTR7; 5-hydroxytryptamine receptor 7 isoform X1 [KO:K04163]
110205152  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
110208122  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
110209926  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
110214178  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
110199822  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
110223768  KCNN2; small conductance calcium-activated potassium channel protein 2 isoform X1 [KO:K04943]
110194194  KCND2; potassium voltage-gated channel subfamily D member 2 isoform X1 [KO:K04892]
110212406  GABRB2; gamma-aminobutyric acid receptor subunit beta-2 isoform X1 [KO:K05181]
110211370  GABRB1; gamma-aminobutyric acid receptor subunit beta-1 [KO:K05181]
110212845  GABRB3; gamma-aminobutyric acid receptor subunit beta-3 [KO:K05181]
110201486  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014]
110214782  APP; amyloid beta A4 protein isoform X1 [KO:K04520]
110217709  HTR1B; 5-hydroxytryptamine receptor 1B [KO:K04153]
110222321  HTR1A; 5-hydroxytryptamine receptor 1A [KO:K04153]
110206043  HTR1D; 5-hydroxytryptamine receptor 1D [KO:K04153]
110199851  HTR1F; LOW QUALITY PROTEIN: 5-hydroxytryptamine receptor 1F [KO:K04153]
110200900  HTR1E; 5-hydroxytryptamine receptor 1E isoform X1 [KO:K04153]
110223891  HTR5A; 5-hydroxytryptamine receptor 5A [KO:K04161]
110198560  5-hydroxytryptamine receptor 5B-like [KO:K04161]
110216929  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
110218213  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha isoform X1 [KO:K04630]
110206959  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
110193656  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
110200602  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
110202795  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
110213789  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
110204582  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
110204813  GNB5; LOW QUALITY PROTEIN: guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
110195466  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
110217882  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
110209930  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
110223453  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
110202405  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 isoform X1 [KO:K04544]
110198231  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
110202413  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
110212886  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
110214163  GNG14; uncharacterized LOC105372280 homolog [KO:K04347]
110222026  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
110202430  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
110215704  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
110222594  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
110196069  DUSP1; dual specificity protein phosphatase 1 [KO:K21278] [EC:3.1.3.16 3.1.3.48]
110202954  HRAS; GTPase HRas isoform X1 [KO:K02833]
110193352  KRAS; GTPase KRas isoform X1 [KO:K07827]
110219182  NRAS; GTPase NRas [KO:K07828]
110203410  GTPase NRas-like [KO:K07828]
110203411  GTPase HRas-like [KO:K07828]
110202309  GTPase HRas-like [KO:K07828]
110201017  ARAF; LOW QUALITY PROTEIN: serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
110216339  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
110204892  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
110205943  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110214234  CACNA1A; LOW QUALITY PROTEIN: voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
110205247  CACNA1B; LOW QUALITY PROTEIN: voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849]
110220761  KCNJ3; LOW QUALITY PROTEIN: G protein-activated inward rectifier potassium channel 1 [KO:K04997]
110214930  KCNJ6; G protein-activated inward rectifier potassium channel 2 isoform X1 [KO:K05000]
110203104  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
110192579  KCNJ5; G protein-activated inward rectifier potassium channel 4 [KO:K04999]
110197250  TRPC1; short transient receptor potential channel 1 isoform X1 [KO:K04964]
110192273  SLC6A4; sodium-dependent serotonin transporter isoform X1 [KO:K05037]
110215301  LOW QUALITY PROTEIN: sodium-dependent serotonin transporter-like [KO:K05037]
110214802  MAOA; LOW QUALITY PROTEIN: amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
110214856  amine oxidase [flavin-containing] B isoform X1 [KO:K00274] [EC:1.4.3.4]
Compound
C00076  Calcium cation
C00078  L-Tryptophan
C00165  Diacylglycerol
C00219  Arachidonate
C00238  Potassium cation
C00427  Prostaglandin H2
C00575  3',5'-Cyclic AMP
C00584  Prostaglandin E2
C00639  Prostaglandin F2alpha
C00643  5-Hydroxy-L-tryptophan
C00696  Prostaglandin D2
C00780  Serotonin
C00909  Leukotriene A4
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C02165  Leukotriene B4
C02166  Leukotriene C4
C02198  Thromboxane A2
C04822  8(R)-HPETE
C05356  5(S)-HPETE
C05635  5-Hydroxyindoleacetate
C05953  Prostaglandin A2
C05954  Prostaglandin B2
C05955  Prostaglandin C2
C05956  Prostaglandin G2
C05957  Prostaglandin J2
C05963  Thromboxane B2
C05964  11-Dehydro-thromboxane B2
C05965  12(S)-HPETE
C05966  15(S)-HPETE
C14768  5,6-EET
C14769  8,9-EET
C14770  11,12-EET
C14771  14,15-EET
C14772  5,6-DHET
C14773  8,9-DHET
C14774  11,12-DHET
C14775  14,15-DHET
C14812  12(R)-HPETE
C14820  11(R)-HPETE
C14821  9(S)-HPETE
C14823  8(S)-HPETE
Reference
PMID:18676031
  Authors
Millan MJ, Marin P, Bockaert J, Mannoury la Cour C
  Title
Signaling at G-protein-coupled serotonin receptors: recent advances and future research directions.
  Journal
Trends Pharmacol Sci 29:454-64 (2008)
DOI:10.1016/j.tips.2008.06.007
Reference
PMID:16896947
  Authors
Bockaert J, Claeysen S, Becamel C, Dumuis A, Marin P
  Title
Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation.
  Journal
Cell Tissue Res 326:553-72 (2006)
DOI:10.1007/s00441-006-0286-1
Reference
PMID:11916537
  Authors
Raymond JR, Mukhin YV, Gelasco A, Turner J, Collinsworth G, Gettys TW, Grewal JS, Garnovskaya MN
  Title
Multiplicity of mechanisms of serotonin receptor signal transduction.
  Journal
Pharmacol Ther 92:179-212 (2001)
DOI:10.1016/S0163-7258(01)00169-3
Reference
PMID:15034221
  Authors
Noda M, Higashida H, Aoki S, Wada K
  Title
Multiple signal transduction pathways mediated by 5-HT receptors.
  Journal
Mol Neurobiol 29:31-9 (2004)
DOI:10.1385/MN:29:1:31
Reference
PMID:20561690
  Authors
Daubert EA, Condron BG
  Title
Serotonin: a regulator of neuronal morphology and circuitry.
  Journal
Trends Neurosci 33:424-34 (2010)
DOI:10.1016/j.tins.2010.05.005
Reference
PMID:16826372
  Authors
Chameau P, van Hooft JA
  Title
Serotonin 5-HT(3) receptors in the central nervous system.
  Journal
Cell Tissue Res 326:573-81 (2006)
DOI:10.1007/s00441-006-0255-8
Reference
PMID:9651340
  Authors
Tournois C, Mutel V, Manivet P, Launay JM, Kellermann O
  Title
Cross-talk between 5-hydroxytryptamine receptors in a serotonergic cell line. Involvement of arachidonic acid metabolism.
  Journal
J Biol Chem 273:17498-503 (1998)
DOI:10.1074/jbc.273.28.17498
Reference
PMID:19545642
  Authors
Iliff JJ, Jia J, Nelson J, Goyagi T, Klaus J, Alkayed NJ
  Title
Epoxyeicosanoid signaling in CNS function and disease.
  Journal
Prostaglandins Other Lipid Mediat 91:68-84 (2010)
DOI:10.1016/j.prostaglandins.2009.06.004
Reference
PMID:12676358
  Authors
Adayev T, Ray I, Sondhi R, Sobocki T, Banerjee P
  Title
The G protein-coupled 5-HT1A receptor causes suppression of caspase-3 through MAPK and protein kinase Calpha.
  Journal
Biochim Biophys Acta 1640:85-96 (2003)
DOI:10.1016/S0167-4889(03)00023-5
Reference
PMID:11701344
  Authors
Albert PR, Tiberi M
  Title
Receptor signaling and structure: insights from serotonin-1 receptors.
  Journal
Trends Endocrinol Metab 12:453-60 (2001)
DOI:10.1016/S1043-2760(01)00498-2
Reference
PMID:9658404
  Authors
Durham PL, Russo AF
  Title
Serotonergic repression of mitogen-activated protein kinase control of the calcitonin gene-related peptide enhancer.
  Journal
Mol Endocrinol 12:1002-9 (1998)
DOI:10.1210/mend.12.7.0135
Reference
PMID:15710402
  Authors
Robert S, Maillet M, Morel E, Launay JM, Fischmeister R, Mercken L, Lezoualc'h F
  Title
Regulation of the amyloid precursor protein ectodomain shedding by the 5-HT4 receptor and Epac.
  Journal
FEBS Lett 579:1136-42 (2005)
DOI:10.1016/j.febslet.2005.01.010
Reference
PMID:12543273
  Authors
Lezoualc'h F, Robert SJ
  Title
The serotonin 5-HT4 receptor and the amyloid precursor protein processing.
  Journal
Exp Gerontol 38:159-66 (2003)
DOI:10.1016/S0531-5565(02)00157-2
Reference
PMID:11043573
  Authors
Durham PL, Russo AF
  Title
Differential regulation of mitogen-activated protein kinase-responsive genes by the duration of a calcium signal.
  Journal
Mol Endocrinol 14:1570-82 (2000)
DOI:10.1210/mend.14.10.0529
Reference
PMID:9542727
  Authors
Hagberg GB, Blomstrand F, Nilsson M, Tamir H, Hansson E
  Title
Stimulation of 5-HT2A receptors on astrocytes in primary culture opens voltage-independent Ca2+ channels.
  Journal
Neurochem Int 32:153-62 (1998)
DOI:10.1016/S0197-0186(97)00087-9
Reference
  Authors
Nestler EJ, Hyman SE, Malenka RC.
  Title
Molecular neuropharmacology: A foundation for clinical neuroscience
  Journal
The McGraw-Hill Companies, Inc. (2001)
Related
pathway
pcw00380  Tryptophan metabolism
pcw00590  Arachidonic acid metabolism
pcw04020  Calcium signaling pathway
pcw04721  Synaptic vesicle cycle
pcw04976  Bile secretion
KO pathway
ko04726   
LinkDB

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