KEGG   PATHWAY: mcc04730
Entry
mcc04730                    Pathway                                
Name
Long-term depression - Macaca mulatta (rhesus monkey)
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
mcc04730  Long-term depression
mcc04730

Other DBs
GO: 0048169
Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
100424593  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
100424899  [KO:K04632]
100424944  GUCY1B1; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
100429106  GNA12; guanine nucleotide-binding protein subunit alpha-12 isoform X1 [KO:K04346]
100533113  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
114673584  [KO:K12319] [EC:4.6.1.2]
574095  CRHR1; corticotropin-releasing factor receptor 1 precursor [KO:K04578]
574344  GRIA2; glutamate receptor 2 isoform 1 precursor [KO:K05198]
574394  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
693554  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
693612  RYR1; ryanodine receptor 1 isoform X1 [KO:K04961]
693781  NOS1; nitric oxide synthase, brain [KO:K13240] [EC:1.14.13.39]
694066  PPP1R17; protein phosphatase 1 regulatory subunit 17 [KO:K08067]
694289  [KO:K04632]
694725  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
695118  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
696308  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
698396  GRIA3; glutamate receptor 3 isoform X1 [KO:K05199]
698444  IGF1; insulin-like growth factor I precursor [KO:K05459]
698553  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
698569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
698736  GRM1; metabotropic glutamate receptor 1 precursor [KO:K04603]
698830  HRAS; GTPase HRas [KO:K02833]
699310  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
699365  GUCY1A1; guanylate cyclase soluble subunit alpha-1 isoform X2 [KO:K12318] [EC:4.6.1.2]
701195  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
701951  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
702877  CRH; corticoliberin [KO:K05256]
703356  PRKG1; cGMP-dependent protein kinase 1 isoform X2 [KO:K07376] [EC:2.7.11.12]
703669  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
703780  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
704787  GRID2; glutamate receptor ionotropic, delta-2 isoform X1 [KO:K05207]
705680  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
706615  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
706704  GNAZ; guanine nucleotide-binding protein G(z) subunit alpha [KO:K04535]
707169  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
707592  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
707690  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
707977  KRAS; GTPase KRas [KO:K07827]
708227  IGF1R; insulin-like growth factor 1 receptor precursor [KO:K05087] [EC:2.7.10.1]
708714  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
708938  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
708940  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
709089  NRAS; GTPase NRas [KO:K07828]
710326  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
710387  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
710415  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
714117  GRIA1; glutamate receptor 1 precursor [KO:K05197]
716635  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
717764  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
718040  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
718144  GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639]
718291  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A isoform X5 [KO:K04344]
718387  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
718412  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
718418  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
718510  [KO:K16342] [EC:3.1.1.4]
719929  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
720263  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
721649  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
721821  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
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
mcc04020  Calcium signaling pathway
mcc04724  Glutamatergic synapse
KO pathway
ko04730   

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