KEGG   PATHWAY: hsa04730Help
Entry
hsa04730                    Pathway                                

Name
Long-term depression - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
Long-term depression
hsa04730

All organismsOrtholog table
Disease
H00063  
Spinocerebellar ataxia (SCA)
H00577  
Syndromic X-linked mental retardation with epilepsy or seizures
H00699  
Central core disease
H00749  
Episodic ataxias
H00775  
Familial or sporadic hemiplegic migraine
H00833  
Neurodegeneration with brain iron accumulation (NBIA)
H01274  
Growth delay due to insulin-like growth factor I resistance
H01310  
Multi-minicore disease (MmD)
Drug
D00537  
Topiramate (JAN/USAN/INN)
D03591  
Corticorelin acetate (USAN)
D03592  
Corticorelin ovine triflutate (USAN)
D03905  
Corticorelin (human) (JAN)
D04155  
Fenobam (USAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
4842  
NOS1; nitric oxide synthase 1 (neuronal) [KO:K13240] [EC:1.14.13.39]
2977  
GUCY1A2; guanylate cyclase 1, soluble, alpha 2 [KO:K12318] [EC:4.6.1.2]
2982  
GUCY1A3; guanylate cyclase 1, soluble, alpha 3 [KO:K12318] [EC:4.6.1.2]
2983  
GUCY1B3; guanylate cyclase 1, soluble, beta 3 [KO:K12319] [EC:4.6.1.2]
5592  
PRKG1; protein kinase, cGMP-dependent, type I [KO:K07376] [EC:2.7.11.12]
5593  
PRKG2; protein kinase, cGMP-dependent, type II [KO:K07376] [EC:2.7.11.12]
10842  
PPP1R17; protein phosphatase 1, regulatory subunit 17 [KO:K08067]
5519  
PPP2R1B; protein phosphatase 2, regulatory subunit A, beta [KO:K03456]
5518  
PPP2R1A; protein phosphatase 2, regulatory subunit A, alpha [KO:K03456]
5515  
PPP2CA; protein phosphatase 2, catalytic subunit, alpha isozyme [KO:K04382] [EC:3.1.3.16]
5516  
PPP2CB; protein phosphatase 2, catalytic subunit, beta isozyme [KO:K04382] [EC:3.1.3.16]
3265  
HRAS; Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845  
KRAS; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893  
NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
369  
ARAF; v-raf murine sarcoma 3611 viral oncogene homolog [KO:K08845] [EC:2.7.11.1]
673  
BRAF; v-raf murine sarcoma viral oncogene homolog B [KO:K04365] [EC:2.7.11.1]
5894  
RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [KO:K04366] [EC:2.7.11.1]
5604  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  
MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
2895  
GRID2; glutamate receptor, ionotropic, delta 2 [KO:K05207]
2911  
GRM1; glutamate receptor, metabotropic 1 [KO:K04603]
2770  
GNAI1; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 [KO:K04630]
2773  
GNAI3; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 [KO:K04630]
2771  
GNAI2; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 [KO:K04630]
2775  
GNAO1; guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O [KO:K04534]
2781  
GNAZ; guanine nucleotide binding protein (G protein), alpha z polypeptide [KO:K04535]
2778  
GNAS; GNAS complex locus [KO:K04632]
2768  
GNA12; guanine nucleotide binding protein (G protein) alpha 12 [KO:K04346]
10672  
GNA13; guanine nucleotide binding protein (G protein), alpha 13 [KO:K04639]
123745  
PLA2G4E; phospholipase A2, group IVE [KO:K16342] [EC:3.1.1.4]
5321  
PLA2G4A; phospholipase A2, group IVA (cytosolic, calcium-dependent) [KO:K16342] [EC:3.1.1.4]
8681  
JMJD7-PLA2G4B; JMJD7-PLA2G4B readthrough [KO:K16342] [EC:3.1.1.4]
PLA2G4B; phospholipase A2, group IVB (cytosolic) [KO:K16342] [EC:3.1.1.4]
8605  
PLA2G4C; phospholipase A2, group IVC (cytosolic, calcium-independent) [KO:K16342] [EC:3.1.1.4]
283748  
PLA2G4D; phospholipase A2, group IVD (cytosolic) [KO:K16342] [EC:3.1.1.4]
255189  
PLA2G4F; phospholipase A2, group IVF [KO:K16342] [EC:3.1.1.4]
5578  
PRKCA; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
5579  
PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C, gamma [KO:K02677] [EC:2.7.11.13]
2776  
GNAQ; guanine nucleotide binding protein (G protein), q polypeptide [KO:K04634]
2767  
GNA11; guanine nucleotide binding protein (G protein), alpha 11 (Gq class) [KO:K04635]
23236  
PLCB1; phospholipase C, beta 1 (phosphoinositide-specific) [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C, beta 3 (phosphatidylinositol-specific) [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
2890  
GRIA1; glutamate receptor, ionotropic, AMPA 1 [KO:K05197]
2891  
GRIA2; glutamate receptor, ionotropic, AMPA 2 [KO:K05198]
2892  
GRIA3; glutamate receptor, ionotropic, AMPA 3 [KO:K05199]
4067  
LYN; v-yes-1 Yamaguchi sarcoma viral related oncogene homolog [KO:K05854] [EC:2.7.10.2]
773  
CACNA1A; calcium channel, voltage-dependent, P/Q type, alpha 1A subunit [KO:K04344]
3708  
ITPR1; inositol 1,4,5-trisphosphate receptor, type 1 [KO:K04958]
3709  
ITPR2; inositol 1,4,5-trisphosphate receptor, type 2 [KO:K04959]
3710  
ITPR3; inositol 1,4,5-trisphosphate receptor, type 3 [KO:K04960]
6261  
RYR1; ryanodine receptor 1 (skeletal) [KO:K04961]
1392  
CRH; corticotropin releasing hormone [KO:K05256]
1394  
CRHR1; corticotropin releasing hormone receptor 1 [KO:K04578]
3479  
IGF1; insulin-like growth factor 1 (somatomedin C) [KO:K05459]
3480  
IGF1R; 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
  Authors
Ito M.
  Title
The molecular organization of cerebellar long-term depression.
  Journal
Nat Rev Neurosci 3:896-902 (2002)
Reference
  Authors
Ito M.
  Title
Cerebellar long-term depression: characterization, signal transduction, and functional roles.
  Journal
Physiol Rev 81:1143-95 (2001)
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)
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)
Reference
  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)
KO pathway
 

DBGET integrated database retrieval system