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

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

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

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)
Ngef  (neuronal guanine nucleotide exchange factor)


Additional Information