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: (View Article at PubMed) PMID:17143272
DOI: Full-text: DOI:10.1038/nn1811

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.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Cdk5  (cyclin-dependent kinase 5)
Cdk5r1  (cyclin-dependent kinase 5 regulatory subunit 1)
Epha4  (Eph receptor A4)


Additional Information