RGD Reference Report - Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism. - Rat Genome Database

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Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism.

Authors: Fu, WY  Chen, Y  Sahin, M  Zhao, XS  Shi, L  Bikoff, JB  Lai, KO  Yung, WH  Fu, AK  Greenberg, ME  Ip, NY 
Citation: Fu WY, etal., Nat Neurosci. 2007 Jan;10(1):67-76. Epub 2006 Dec 3.
RGD ID: 8554385
Pubmed: PMID:17143272   (View Abstract at PubMed)
DOI: DOI:10.1038/nn1811   (Journal Full-text)

The development of dendritic spines is thought to be crucial for synaptic plasticity. Dendritic spines are retracted upon Eph receptor A4 (EphA4) activation, but the mechanisms that control this process are not well understood. Here we report an important function of cyclin-dependent kinase 5 (Cdk5) in EphA4-dependent spine retraction in mice. We found that blocking Cdk5 activity inhibits ephrin-A1-triggered spine retraction and reduction of mEPSC frequency at hippocampal synapses. The activation of EphA4 resulted in the recruitment of Cdk5 to EphA4, leading to the tyrosine phosphorylation and activation of Cdk5. EphA4 and Cdk5 then enhanced the activation of ephexin1, a guanine-nucleotide exchange factor that regulates activation of the small Rho GTPase RhoA. The association between EphA4 and ephexin1 was significantly reduced in Cdk5(-/-) brains and Cdk5-dependent phosphorylation of ephexin1 was required for the ephrin-A1-mediated regulation of spine density. These findings suggest that ephrin-A1 promotes EphA4-dependent spine retraction through the activation of Cdk5 and ephexin1, which in turn modulates actin cytoskeletal dynamics.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cdk5Ratregulation of synapse pruning involved_inEXP PMID:17143272SynGO 
Cdk5Ratregulation of synapse pruning involved_inIDA PMID:17143272SynGO 
Cdk5Ratregulation of synapse pruning involved_inIMP PMID:17143272SynGO 
Epha4Ratregulation of synapse pruning involved_inIMP PMID:17143272SynGO 
Epha4Ratregulation of synapse pruning involved_inIEP PMID:17143272SynGO 
Epha4Ratregulation of synapse pruning involved_inIDA PMID:17143272SynGO 
Epha4Ratregulation of synapse pruning involved_inEXP PMID:17143272SynGO 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cdk5Ratglutamatergic synapse is_active_inEXP PMID:17143272SynGO 
Cdk5Ratglutamatergic synapse is_active_inIDA PMID:17143272SynGO 
Cdk5Ratglutamatergic synapse is_active_inIMP PMID:17143272SynGO 
Epha4Ratglutamatergic synapse is_active_inIMP PMID:17143272SynGO 
Epha4Ratglutamatergic synapse is_active_inIEP PMID:17143272SynGO 
Epha4Ratglutamatergic synapse is_active_inIDA PMID:17143272SynGO 
Epha4Ratglutamatergic synapse is_active_inEXP PMID:17143272SynGO 
Epha4Ratplasma membrane located_inIDA PMID:17143272UniProt 
NgefRatpostsynapse is_active_inIDA PMID:17143272SynGO 
Cdk5Ratpostsynaptic density located_inIDA PMID:17143272UniProt 
Cdk5r1Ratpostsynaptic density located_inIDA PMID:17143272UniProt 
Epha4Ratpostsynaptic density located_inIDA PMID:17143272UniProt 
Cdk5RatSchaffer collateral - CA1 synapse is_active_inEXP PMID:17143272SynGO 
Cdk5RatSchaffer collateral - CA1 synapse is_active_inIDA PMID:17143272SynGO 
Cdk5RatSchaffer collateral - CA1 synapse is_active_inIMP PMID:17143272SynGO 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cdk5Ratephrin receptor binding enablesIPIUniProtKB:D3ZZK3PMID:17143272UniProt 
Cdk5r1Ratephrin receptor binding enablesIPIUniProtKB:D3ZZK3PMID:17143272UniProt 
Epha4Ratprotein binding enablesIPIUniProtKB:P61810PMID:17143272UniProt 
Epha4Ratprotein binding enablesIPIUniProtKB:Q03114PMID:17143272UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Cdk5  (cyclin-dependent kinase 5)
Cdk5r1  (cyclin-dependent kinase 5 regulatory subunit 1)
Epha4  (Eph receptor A4)
Ngef  (neuronal guanine nucleotide exchange factor)


Additional Information