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

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

Authors

  • Odajima J
  • Wills ZP
  • Ndassa YM
  • Terunuma M
  • Kretschmannova K
  • Deeb TZ
  • Geng Y
  • Gawrzak S
  • Quadros IM
  • Newman J
  • Das M
  • Jecrois ME
  • Yu Q
  • Li N
  • Bienvenu F
  • Moss SJ
  • Greenberg ME
  • Marto JA
  • Sicinski P

Journal

Developmental cell

Publication Data

October 18, 2011

Associated Grants

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

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