KEGG   PATHWAY: ko04730Help
Entry
ko04730                     Pathway                                

Name
Long-term depression
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
ko04730

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)
Other DBs
BSID: 
GO: 
Orthology
K13240  
nitric-oxide synthase, brain [EC:1.14.13.39]
K12318  
guanylate cyclase soluble subunit alpha [EC:4.6.1.2]
K12319  
guanylate cyclase soluble subunit beta [EC:4.6.1.2]
K07376  
protein kinase, cGMP-dependent [EC:2.7.11.12]
K08067  
protein phosphatase 1 regulatory subunit 17
K03456  
serine/threonine-protein phosphatase 2A regulatory subunit A
K04382  
serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16]
K02833  
GTPase HRas
K07827  
GTPase KRas
K07828  
GTPase NRas
K08845  
A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04365  
B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  
RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  
mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  
mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  
mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K05207  
glutamate receptor delta-2 subunit
K04603  
metabotropic glutamate receptor 1
K04630  
guanine nucleotide-binding protein G(i) subunit alpha
K04534  
guanine nucleotide-binding protein G(o) subunit alpha
K04535  
guanine nucleotide-binding protein G(z) subunit alpha
K04632  
guanine nucleotide-binding protein G(s) subunit alpha
K04346  
guanine nucleotide-binding protein subunit alpha-12
K04639  
guanine nucleotide-binding protein subunit alpha-13
K16342  
cytosolic phospholipase A2 [EC:3.1.1.4]
K02677  
classical protein kinase C [EC:2.7.11.13]
K04634  
guanine nucleotide-binding protein G(q) subunit alpha
K04635  
guanine nucleotide-binding protein subunit alpha-11
K05858  
phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K05197  
glutamate receptor 1
K05198  
glutamate receptor 2
K05199  
glutamate receptor 3
K05854  
tyrosine-protein kinase Lyn [EC:2.7.10.2]
K04344  
voltage-dependent calcium channel P/Q type alpha-1A
K04958  
inositol 1,4,5-triphosphate receptor type 1
K04959  
inositol 1,4,5-triphosphate receptor type 2
K04960  
inositol 1,4,5-triphosphate receptor type 3
K04961  
ryanodine receptor 1
K05256  
corticotropin-releasing hormone
K04578  
corticotropin releasing hormone receptor 1
K05459  
insulin-like growth factor 1
K05087  
insulin-like growth factor 1 receptor [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)

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