KEGG   PATHWAY: ssc04730
Entry
ssc04730                    Pathway                                
Name
Long-term depression - Sus scrofa (pig)
Description
Cerebellar long-term depression (LTD), thought to be a molecular and cellular basis for cerebellar learning, is a process involving a decrease in the synaptic strength between parallel fiber (PF) and Purkinje cells (PCs) induced by the conjunctive activation of PFs and climbing fiber (CF). Multiple signal transduction pathways have been shown to be involved in this process. Activation of PFs terminating on spines in dendritic branchlets leads to glutamate release and activation of both AMPA and mGluRs. Activation of CFs, which make multiple synaptic contacts on proximal dendrites, also via AMPA receptors, opens voltage-gated calcium channels (VGCCs) and causes a generalized influx of calcium. These cellular signals, generated from two different synaptic origins, trigger a cascade of events culminating in a phosphorylation-dependent, long-term reduction in AMPA receptor sensitivity at the PF-PC synapse. This may take place either through receptor internalization and/or through receptor desensitization.
Class
Organismal Systems; Nervous system
Pathway map
ssc04730  Long-term depression
ssc04730

Other DBs
GO: 0048169
Organism
Sus scrofa (pig) [GN:ssc]
Gene
100520934  NOS1; nitric oxide synthase, brain isoform X1 [KO:K13240] [EC:1.14.13.39]
553100  GUCY1A3; guanylate cyclase soluble subunit alpha-3 [KO:K12318] [EC:4.6.1.2]
100522091  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
444999  GUCY1B3; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
100625149  guanylate cyclase soluble subunit beta-2 [KO:K12319] [EC:4.6.1.2]
733640  PRKG1; cGMP-dependent protein kinase 1 [KO:K07376] [EC:2.7.11.12]
100512796  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
100511608  PPP1R17; protein phosphatase 1 regulatory subunit 17 [KO:K08067]
397088  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
397470  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X3 [KO:K03456]
397656  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
397136  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
110259208  HRAS; GTPase HRas isoform X1 [KO:K02833]
100518251  KRAS; GTPase KRas isoform X2 [KO:K07827]
100739349  NRAS; GTPase NRas precursor [KO:K07828]
397601  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
100514612  BRAF; serine/threonine-protein kinase B-raf isoform X6 [KO:K04365] [EC:2.7.11.1]
100737448  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100233191  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100525505  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100153927  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
445013  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100516747  GRID2; LOW QUALITY PROTEIN: glutamate receptor ionotropic, delta-2 [KO:K05207]
100625610  GRM1; metabotropic glutamate receptor 1 isoform X2 [KO:K04603]
100144421  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
100144419  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
397523  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
100516976  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
100151867  GNAZ; guanine nucleotide-binding protein G(z) subunit alpha isoform X1 [KO:K04535]
100049657  GNAS; SCG6 (secretogranin VI) isoform SCG6 [KO:K04632]
100525156  GNA12; guanine nucleotide-binding protein subunit alpha-12 isoform X1 [KO:K04346]
100522824  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
100520687  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
100152927  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
100514811  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
100513834  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
102162529  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
397184  PRKCA; LOW QUALITY PROTEIN: protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100522792  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
100518074  PRKCG; protein kinase C gamma type isoform X3 [KO:K19663] [EC:2.7.11.13]
654405  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
733588  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
100152679  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
100157641  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
100516581  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100525148  PLCB3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100623647  GRIA1; glutamate receptor 1 isoform X1 [KO:K05197]
100622950  GRIA2; glutamate receptor 2 isoform X2 [KO:K05198]
100519996  GRIA3; glutamate receptor 3 isoform X2 [KO:K05199]
100152890  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
100525387  CACNA1A; LOW QUALITY PROTEIN: voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
397454  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
100517279  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
100155015  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
396718  RYR1; ryanodine receptor 1 [KO:K04961]
100127468  CRH; corticoliberin precursor [KO:K05256]
397426  CRHR1; corticotropin-releasing factor receptor 1 precursor [KO:K04578]
397491  IGF1; insulin-like growth factor I precursor [KO:K05459]
397350  IGF1R; insulin-like growth factor 1 receptor precursor [KO:K05087] [EC:2.7.10.1]
Compound
C00025  L-Glutamate
C00076  Calcium cation
C00165  Diacylglycerol
C00219  Arachidonate
C00533  Nitric oxide
C00641  1,2-Diacyl-sn-glycerol
C00942  3',5'-Cyclic GMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
Reference
PMID:12415297
  Authors
Ito M.
  Title
The molecular organization of cerebellar long-term depression.
  Journal
Nat Rev Neurosci 3:896-902 (2002)
DOI:10.1038/nrn962
Reference
PMID:11427694
  Authors
Ito M.
  Title
Cerebellar long-term depression: characterization, signal transduction, and functional roles.
  Journal
Physiol Rev 81:1143-95 (2001)
DOI:10.1152/physrev.2001.81.3.1143
Reference
  Authors
Purves D, Augustine GJ (ed).
  Title
Neuroscience
  Journal
Sunderland, Mass.:Sinauer Associates (2004)
Reference
PMID:9735948
  Authors
Daniel H, Levenes C, Crepel F.
  Title
Cellular mechanisms of cerebellar LTD.
  Journal
Trends Neurosci 21:401-7 (1998)
DOI:10.1016/S0166-2236(98)01304-6
Reference
PMID:9602501
  Authors
Levenes C, Daniel H, Crepel F.
  Title
Long-term depression of synaptic transmission in the cerebellum: cellular and molecular mechanisms revisited.
  Journal
Prog Neurobiol 55:79-91 (1998)
DOI:10.1016/S0301-0082(97)00096-8
Reference
PMID:14509570
  Authors
Metzger F, Kapfhammer JP.
  Title
Protein kinase C: its role in activity-dependent Purkinje cell dendritic development and plasticity.
  Journal
Cerebellum 2:206-14 (2003)
DOI:10.1080/14734220310016150
Related
pathway
ssc04020  Calcium signaling pathway
ssc04724  Glutamatergic synapse
KO pathway
ko04730   
LinkDB

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