Nedd9 Protein, a Cas-L Homologue, Is Upregulated After Transient Global Ischemia in Rats: Possible Involvement of Nedd9 in the Differentiation of Neurons After Ischemia
Nedd9 Protein, a Cas-L Homologue, Is Upregulated After Transient Global Ischemia in Rats: Possible Involvement of Nedd9 in the Differentiation of Neurons After Ischemia
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DOI：
10.1161/01.str.0000185672.10390.30
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发表时间：
2005-11
期刊：
影响因子：
8.3
通讯作者：
Takahiro Sasaki;S. Iwata;H. Okano;Y. Urasaki;Junichi Hamada;Hirotoshi Tanaka;N. Dang;H. Okano;C. Morimoto
中科院分区：
文献类型：
--
作者：
Takahiro Sasaki;S. Iwata;H. Okano;Y. Urasaki;Junichi Hamada;Hirotoshi Tanaka;N. Dang;H. Okano;C. Morimoto
背景和目的-一些参与成年脑卒中后自我修复的蛋白质主要在胚胎发育期表达，在出生后早期表达强烈下调。神经元前体细胞表达的发育下调基因（Nedd）9被认为与Crk相关底物淋巴细胞类型（Cas-L）相同，Cas-L是一种与多种信号分子（如粘着斑激酶（FAK），富含脯氨酸的酪氨酸激酶2（Pyk 2）和Crk）相关的对接蛋白。我们研究了这些蛋白质参与全脑缺血的病理生理学。方法：克隆小鼠Cas-L/Nedd 9 cDNA。采用RT-PCR、Western blot和免疫组织化学方法研究了Cas-L/Nedd 9蛋白在大鼠全脑缺血中的表达及作用。还评估了Nedd 9缺失突变体的转染子在PC-12细胞中的神经突生长，以阐明Nedd 9蛋白的功能。结果-Nedd 9是Cas-L的剪接变体，并且在缺血后1至14天在大脑皮层和海马的神经元中被选择性地诱导。缺血后神经元树突和索马体中Nedd 9蛋白被酪氨酸磷酸化并与FAK结合。最后，证明Nedd 9促进PC-12细胞的神经突生长。结论：我们的研究可能支持Nedd 9参与大鼠全脑缺血后神经元分化的潜力。
Background and Purpose— Some proteins involved in self-repair after stroke in the adult brain are primarily expressed during embryonic development and strongly down-regulated during the early postnatal phase. Neuronal precursor cell-expressed, developmentally down-regulated gene (Nedd) 9 was recognized to be identical to Crk-associated substrate lymphocyte type (Cas-L), a docking protein that associates with a variety of signaling molecules, such as focal adhesion kinase (FAK), proline-rich tyrosine kinase 2 (Pyk2), and Crk. We investigated the involvement of these proteins in the pathophysiology of global cerebral ischemia. Methods— The mouse Cas-L/Nedd9 cDNAs were cloned. The expression and function of Cas-L/Nedd9 protein in the pathogenesis of global ischemia in rats was investigated by RT-PCR, Western blot analysis, and immunohistochemistry. The neurite outgrowth of the transfectants of Nedd9 deletion mutants in PC-12 cells was also assessed to clarify the function of the Nedd9 protein. Results— Nedd9 was a splicing variant of Cas-L and was selectively induced in neurons of the cerebral cortex and hippocampus 1 to 14 days after the ischemia. Induced Nedd9 protein was tyrosine phosphorylated and was bound to FAK in dendrite and soma of neurons after the ischemia. Finally, it was demonstrated that Nedd9 promoted neurite outgrowth of PC-12 cells. Conclusions— Our study may support the potential of Nedd9 for participation in the differentiation of neurons after global ischemia in rats.