title: Cyclin E constrains Cdk5 activity to regulate synaptic plasticity and memory formation.
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 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.
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors.forename: Junko
authors.initials: J
authors.lastname: Odajima
authors.forename: Zachary P
authors.initials: ZP
authors.lastname: Wills
authors.forename: Yasmine M
authors.initials: YM
authors.lastname: Ndassa
authors.forename: Miho
authors.initials: M
authors.lastname: Terunuma
authors.forename: Karla
authors.initials: K
authors.lastname: Kretschmannova
authors.forename: Tarek Z
authors.initials: TZ
authors.lastname: Deeb
authors.forename: Yan
authors.initials: Y
authors.lastname: Geng
authors.forename: Sylwia
authors.initials: S
authors.lastname: Gawrzak
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Quadros
authors.forename: Jennifer
authors.initials: J
authors.lastname: Newman
authors.forename: Manjusri
authors.initials: M
authors.lastname: Das
authors.forename: Marie E
authors.initials: ME
authors.lastname: Jecrois
authors.forename: Qunyan
authors.initials: Q
authors.lastname: Yu
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Frederic
authors.initials: F
authors.lastname: Bienvenu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Moss
authors.forename: Michael E
authors.initials: ME
authors.lastname: Greenberg
authors.forename: Jarrod A
authors.initials: JA
authors.lastname: Marto
authors.forename: Piotr
authors.initials: P
authors.lastname: Sicinski
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D019927:Cyclin E / Q000502:physiology*; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics* / Q000378:metabolism; D049229:Dendritic Spines / Q000502:physiology*; D004594:Electrophysiology; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus; D007124:Immunoenzyme Techniques; D019426:Integrases / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009924:Organ Culture Techniques; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013569:Synapses / Q000378:metabolism*
chemical_list: D019927:Cyclin E; D008156:Luciferases; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; C045073:Cre recombinase; D019426:Integrases