KEGG   PATHWAY: mlf04730
Entry
mlf04730                    Pathway                                
Name
Long-term depression - Myotis lucifugus (little brown bat)
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
mlf04730  Long-term depression
mlf04730

Other DBs
GO: 0048169
Organism
Myotis lucifugus (little brown bat) [GN:mlf]
Gene
102433074  NOS1; nitric oxide synthase, brain [KO:K13240] [EC:1.14.13.39]
102417646  GUCY1A1; guanylate cyclase soluble subunit alpha-3 [KO:K12318] [EC:4.6.1.2]
102429123  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
102428541  guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
102442918  GUCY1B1; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:4.6.1.2]
102423140  PRKG2; cGMP-dependent protein kinase 2 isoform X1 [KO:K19477] [EC:2.7.11.12]
102432083  PPP1R17; protein phosphatase 1 regulatory subunit 17 isoform X1 [KO:K08067]
102421388  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
102442817  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
102432188  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
102430803  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
102431999  KRAS; GTPase KRas isoform X1 [KO:K07827]
102430744  NRAS; GTPase NRas [KO:K07828]
102420799  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
102435241  BRAF; LOW QUALITY PROTEIN: serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
102434453  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102417411  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
102423748  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102417755  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102422236  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102442423  GRID2; glutamate receptor ionotropic, delta-2 [KO:K05207]
102428336  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
102427230  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
102429580  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
102431273  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
102438598  guanine nucleotide-binding protein G(o) subunit alpha-like [KO:K04534]
102428502  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X11 [KO:K04632]
102433989  neuroendocrine secretory protein 55-like [KO:K04632]
102436989  GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X2 [KO:K04639]
102422494  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
102424085  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
102419721  cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
102420552  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
102422798  PLA2G4F; LOW QUALITY PROTEIN: cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
102438932  PRKCA; protein kinase C alpha type isoform X2 [KO:K02677] [EC:2.7.11.13]
102428240  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
102419083  protein kinase C gamma type-like [KO:K19663] [EC:2.7.11.13]
102424688  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102424028  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
102432706  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
102438291  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
102432440  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
102429686  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
102441813  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858] [EC:3.1.4.11]
102421761  GRIA1; glutamate receptor 1 isoform X1 [KO:K05197]
102441353  GRIA2; glutamate receptor 2 isoform X3 [KO:K05198]
102438664  GRIA3; glutamate receptor 3 isoform X1 [KO:K05199]
102429660  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
102423622  CACNA1A; LOW QUALITY PROTEIN: voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
102422734  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102442861  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102437305  RYR1; LOW QUALITY PROTEIN: ryanodine receptor 1 [KO:K04961]
102421075  CRH; corticoliberin [KO:K05256]
102426185  CRHR1; corticotropin-releasing factor receptor 1 isoform X4 [KO:K04578]
102424041  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
102430595  IGF1R; LOW QUALITY PROTEIN: insulin-like growth factor 1 receptor [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
mlf04020  Calcium signaling pathway
mlf04724  Glutamatergic synapse
KO pathway
ko04730   
LinkDB

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