Localization and developmental changes in the neuron-specific cyclin-dependent kinase 5 activator (p35nck5a) in the rat brain
Localization and developmental changes in the neuron-specific cyclin-dependent kinase 5 activator (p35nck5a) in the rat brain
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大鼠脑中神经元特异性细胞周期蛋白依赖性激酶 5 激活剂 (p35nck5a) 的定位和发育变化
DOI：
10.1016/0306-4522(96)00136-4
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发表时间：
1996
期刊：
影响因子：
3.3
通讯作者：
O. Hatase
中科院分区：
文献类型：
--
作者：
K. Tomizawa;H. Matsui;M. Matsushita;J. Lew;M. Tokuda;T. Itano;R. Konishi;Jerry H. Wang;O. Hatase
哺乳动物大脑含有cdc2样蛋白激酶，它是细胞周期蛋白依赖性激酶5 (Cdk5)的异二聚体，以及分子量为35,000的大脑特异性调节亚基，名为p35nck5a。 Cdk5 已被确定为大脑中 tau 蛋白的主要磷酸化酶。在这项研究中，我们检查了发育中的大鼠大脑中 p35nck5a 的时间和空间表达模式。 Northern印迹分析显示，交配后12天的大鼠大脑中p35nck5amessenger RNA表达较低，交配后18天至出生后两周升高至较高水平，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 p35nck5ai 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，p35nck5a 蛋白存在于有丝分裂后神经元中，但不存在于大脑发育所有阶段的神经胶质细胞中，表明 p35nck5a 是一种神经元特异性蛋白。在成人大脑中，这种蛋白质在细胞体和树突中含量丰富，而在轴突中只检测到非常少量的蛋白质。然而，在胎儿和新生儿大脑中，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，p35nck5ai 是神经元特异性的，也是 Cdk5 的特异性激活剂，并且两者的亚细胞定位受到大脑发育的严格调节。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发挥关键作用。
Mammalian brains contain a cdc2-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, named p35nck5a. Cdk5 has been identified as the major phosphorylating enzyme of tau protein in the brain. In this study, we examined the temporal and spatial expression patterns of p35nck5ain the developing rat brain. Northern blot analysis showed that p35nck5amessenger RNA expression was low in the brain of 12-day postcoitum rats, and increased to a much higher level from 18days postcoitum to two weeks after birth, and then declined at three weeks after birth. These developmental changes in p35nck5aexpression correlated with the changes in Cdk5-associated kinase activity during brain development. These data suggest that p35nck5ais the specific activator for Cdk5 in the brain. Immunohistochemical and in situ hybridization studies demonstrated the presence of p35nck5aprotein in postmitotic neurons but not in glial cells at all stages of brain development, indicating that p35nck5ais 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-p35nck5aantibody. Our findings suggest that p35nck5ais 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.
DOI：
10.1073/pnas.82.12.4274
发表时间：
1985-01-01
影响因子：
11.1
作者：
STERNBERGER, NH;STERNBERGER, LA;ULRICH, J
通讯作者：
ULRICH, J
阿尔茨海默病缠结与两种大神经丝蛋白中的多磷酸化重复具有免疫学相似性。
DOI：
10.1073/pnas.85.19.7384
发表时间：
1988
影响因子：
11.1
作者：
Lee,VM;OtvosJr,L;Schmidt,ML;Trojanowski,JQ
通讯作者：
Trojanowski,JQ