KEGG PATHWAY: hsa04730

PATHWAY: hsa04730

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

Pathway map

hsa04730

Long-term depression

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:

83086

GO:

0048169

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; v-Ha-ras Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845	KRAS; v-Ki-ras2 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 B1 [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]
100137049	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

PMID:12415297

Authors

Ito M.

Title

The molecular organization of cerebellar long-term depression.

Journal

Nat Rev Neurosci 3:896-902 (2002)

Reference

PMID:11427694

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

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)

KO pathway

ko04730

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Ontology (3)   
   KEGG BRITE (3)   
Pathway (1)   
   BioSystems (1)   
Disease (8)   
   KEGG DISEASE (8)   
Drug (5)   
   KEGG DRUG (5)   
Genome (1)   
   KEGG GENOME (1)   
Gene (60)   
   KEGG GENES (60)   
All databases (78)   

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