[Expression of cyclin E in postmitotic cells in the central nervous system]

Cyclin E, a member of G1 cyclins, is expressed specifically at the G1 to S phase in proliferating cells and promotes the entry into S phase by binding and activating a specific cyclin-dependent kinase, cdk2. To investigate the regulatory mechanisms of the cell cycle in the developing central nervous system (CNS), this study was conducted to analyze expression of cyclin E and other G1 cyclins/cdks in the developing and adult mice and rats. Western blotting and in situ hybridization indicate that both mRNA and protein of cyclin E are expressed in the developing CNS, and are also detected in adulthood when no expression of other G1 cyclins and cdks is observed. Immunohistochemical analysis reveals that, during development of the cerebral cortex, cyclin E protein is expressed not only in proliferating regions but also in differentiating regions where cells are mitotically negative, and that subcellular localization of cyclin E protein changes from the nucleus to the cytoplasm during postnatal development of CNS. Cyclin E forms a complex with cdk5 which is activated by a neuron-specific regulatory subunit, p35, and cyclin E/cdk5 complex was detected mainly in the cytoplasm, although no cyclin E-associated kinase activity was detected in the adult CNS. These results indicate that cyclin E is expressed in terminally differentiated neurons which are already withdrawn from the cell cycle, and suggest a novel role for cyclin E in postmitotic neurons in the CNS in addition to its role in cell cycle regulation in proliferating neuroblasts.