Tomizawa K, Matsui H, Matsushita M, Lew J, Tokuda M, Itano T, Konishi R, Wang J H, Hatase O
First Department of Physiology, Okayama University Medical School, Japan.
Neuroscience. 1996 Sep;74(2):519-29. doi: 10.1016/0306-4522(96)00136-4.
Mammalian brains contain a cde2-like protein kinase which is a heterodimer of cyclin-dependent kinase 5 (Cdk5) and a brain-specific regulatory subunit with a molecular weight of 35,000. In this study, we examined the temporal and spatial expression patterns of p35nck5a in the developing rat brain. Northern blot analysis showed that p35nck5a messenger RNA expression was low in the brain of 12-day postcoitum rats, and increased to a much higher level from 18 days postcoitum to two weeks after birth, and then declined at three weeks after birth. These developmental changes in p35nck5a expression correlated with the changes in Cdk5-associated kinase activity during brain development. These data suggest that p35nck5a is the specific activator for Cdk5 in the brain. Immunohistochemical and in situ hybridization studies demonstrated the presence of p35nck5a protein in postmitotic neurons but not in glial cells at all stages of brain development, indicating that p35nck5a is a neuron-specific protein. In the adult brain, the protein was rich in cell bodies and dendrites, and only very low amounts were detected in axons. In fetal and neonatal brains, however, axonal pathways such as the corpus callosum and external capsule were also stained with anti-p35nck5a antibody. Our findings suggest that p35nck5a is neuron specific, and a specific activator for Cdk5, and the subcellular localization of the two is strictly regulated depending on brain development. Neuronal Cdc2-like kinase may play key roles in neuronal maturation, synaptic formation, and neuronal plasticity.
哺乳动物的大脑含有一种cde2样蛋白激酶，它是细胞周期蛋白依赖性激酶5（Cdk5）与一种分子量为35000的脑特异性调节亚基组成的异二聚体。在本研究中，我们检测了p35nck5a在发育中的大鼠大脑中的时空表达模式。Northern印迹分析表明，在产后12天大鼠的大脑中，p35nck5a信使核糖核酸的表达较低，从产后18天到出生后两周增加到高得多的水平，然后在出生后三周下降。p35nck5a表达的这些发育变化与大脑发育过程中Cdk5相关激酶活性的变化相关。这些数据表明p35nck5a是大脑中Cdk5的特异性激活剂。免疫组织化学和原位杂交研究表明，在大脑发育的所有阶段，有丝分裂后神经元中存在p35nck5a蛋白，而神经胶质细胞中则完全没有，这表明p35nck5a是一种神经元特异性蛋白。在成体大脑中，该蛋白在细胞体和树突中含量丰富，而在轴突中仅检测到极少量。然而，在胎儿和新生儿大脑中，诸如胼胝体和外囊等轴突通路也被抗p35nck5a抗体染色。我们的研究结果表明，p35nck5a是神经元特异性的，是Cdk5的特异性激活剂，并且两者的亚细胞定位根据大脑发育受到严格调控。神经元Cdc2样激酶可能在神经元成熟、突触形成和神经元可塑性中起关键作用。
