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Cyclin E constrains Cdk5 activity to regulate synaptic plasticity and memory formation.

Developmental cell | Oct 18, 2011

Cyclin E is a component of the core cell cycle machinery, and it drives cell proliferation by regulating entry and progression of cells through the DNA synthesis phase. Cyclin E expression is normally restricted to proliferating cells. However, high levels of cyclin E are expressed in the adult brain. The function of cyclin E in quiescent, postmitotic nervous system remains unknown. Here we use a combination of in vivo quantitative proteomics and analyses of cyclin E knockout mice to demonstrate that in terminally differentiated neurons cyclin E forms complexes with Cdk5 and controls synapse function by restraining Cdk5 activity. Ablation of cyclin E led to a decreased number of synapses, reduced number and volume of dendritic spines, and resulted in impaired synaptic plasticity and memory formation in cyclin E-deficient animals. These results reveal a cell cycle-independent role for a core cell cycle protein, cyclin E, in synapse function and memory.

Pubmed ID: 21944720 RIS Download

Mesh terms: Animals | Behavior, Animal | Blotting, Western | Brain | Cells, Cultured | Cyclin E | Cyclin-Dependent Kinase 5 | Dendritic Spines | Electrophysiology | Embryo, Mammalian | Female | Gene Expression Regulation, Developmental | Hippocampus | Immunoenzyme Techniques | Integrases | Luciferases | Male | Memory | Mice | Mice, Knockout | Neurons | Organ Culture Techniques | Proteomics | Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization | Synapses

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Associated grants

  • Agency: NINDS NIH HHS, Id: R01 NS081986
  • Agency: NCI NIH HHS, Id: R01 CA108950
  • Agency: NINDS NIH HHS, Id: R01 NS051195
  • Agency: NINDS NIH HHS, Id: R01 NS045500
  • Agency: NCI NIH HHS, Id: R01 CA108950-07

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