Cyclin E constrains Cdk5 activity to regulate synaptic plasticity and memory formation.
Journal:
Dev. Cell 2011 OctAuthors:
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
Abstract
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 demonstrat
...[more]e 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.[less]
Mesh Headings:
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