Matsushita M, Matsui H, Itano T, Tomizawa K, Tokuda M, Suwaki H, Wang J H, Hatase O
Department of Neuropsychiatry, Kagawa Medical School, Japan.
Neuroreport. 1995 Jun 19;6(9):1267-70. doi: 10.1097/00001756-199506090-00009.
Cyclin dependent kinase 5 (Cdk5) phosphorylates tau protein, a microtubule-associated protein, at pathological sites in vitro as well as in Alzheimer's disease brain. The enzyme is therefore regarded as an important candidate responsible for the progression of Alzheimer's disease. We and others have suggested that the enzyme has physiological roles in brain development and maturation. In this study, we investigated the exact distribution and developmental changes of the enzyme in cerebellum by immunohistochemistry and non-radioactive in situ hybridization. Immunohistochemistry demonstrated that Cdk5 was consistently expressed in the cerebellum at all developing stages. However, the subcellular localization of Cdk5 dramatically changed during maturation of the cerebellum. In the early neonatal stage, Cdk5 was strongly expressed in the cell bodies of neurones. With neuronal maturation Cdk5 immunoreactivity changed its subcellular localization from the cell body to axon. In terminally differentiated neurons, the immunoreactivity was only detected in the axon. These results suggest that subcellular localization of Cdk5 is strictly regulated and may play an important role in neuronal maturation.
细胞周期蛋白依赖性激酶5（Cdk5）可在体外以及阿尔茨海默病患者的大脑中的病理位点使微管相关蛋白tau蛋白发生磷酸化。因此，该酶被视为导致阿尔茨海默病进展的重要候选因素。我们和其他人都认为该酶在大脑发育和成熟过程中具有生理作用。在本研究中，我们通过免疫组织化学和非放射性原位杂交技术研究了该酶在小脑中的确切分布和发育变化。免疫组织化学显示，Cdk5在小脑发育的各个阶段均持续表达。然而，在小脑成熟过程中，Cdk5的亚细胞定位发生了显著变化。在新生儿早期，Cdk5在神经元细胞体中强烈表达。随着神经元成熟，Cdk5免疫反应性的亚细胞定位从细胞体转移到轴突。在终末分化的神经元中，仅在轴突中检测到免疫反应性。这些结果表明，Cdk5的亚细胞定位受到严格调控，可能在神经元成熟中发挥重要作用。
