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.

journal_name

Dev Cell

journal_title

Developmental cell

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

doi

10.1016/j.devcel.2011.08.009

subject

Has Abstract

pub_date

2011-10-18 00:00:00

pages

655-68

issue

4

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(11)00347-9

journal_volume

21

pub_type

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