Mi Yajing, Gao Xingchun, Ma Yue, Gao Jie, Wang Zhen, Jin Weilin
Institute of Basic Medicine Science, Xi'an Medical University, Xi'an 710021, China; School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Institute of Basic Medicine Science, Xi'an Medical University, Xi'an 710021, China.
Int J Biochem Cell Biol. 2014 Dec;57:1-6. doi: 10.1016/j.biocel.2014.09.024. Epub 2014 Oct 5.
Oligodendrocyte-derived neurite-outgrowth inhibitor Nogo-A and its restriction mechanism are well-known. Recently, Nogo-A is reported to be abundantly expressed in neurons, however, the concrete link between neuronal Nogo-A and neuronal development is poorly understood. In the present study, we used Neuro2A and COS7 cell lines to clarify that Nogo-A largely distributed in the centrosome and microtubules-rich regions. When endogenous Nogo-A was down-regulated with RNA interference, the percentage of cell differentiation and the total neurite length of Neuro2A exposed to valproic acid (VPA) decreased sharply. Furthermore, in primary neurons, acetylated α-tubulin decreased at the tips of neurites where endogenous Nogo-A was still highly expressed. In HEK293FT cell lines, Nogo-A overexpression could redistribute acetylated α-tubulin but not change the level of α-tubulin. Together, our data discovered that centrosome- and microtubules-localized Nogo-A positively regulates neuronal differentiation and neurite outgrowth of Neuro2A cell lines, implicating the essential roles of subcellular Nogo-A in neuronal development.
少突胶质细胞衍生的轴突生长抑制因子Nogo - A及其限制机制已广为人知。最近，有报道称Nogo - A在神经元中大量表达，然而，神经元Nogo - A与神经元发育之间的具体联系却知之甚少。在本研究中，我们使用Neuro2A和COS7细胞系来阐明Nogo - A主要分布在中心体和富含微管的区域。当通过RNA干扰下调内源性Nogo - A时，暴露于丙戊酸（VPA）的Neuro2A细胞的分化百分比和总轴突长度急剧下降。此外，在原代神经元中，内源性Nogo - A仍高度表达的轴突末端乙酰化α - 微管蛋白减少。在HEK293FT细胞系中，Nogo - A的过表达可重新分布乙酰化α - 微管蛋白，但不会改变α - 微管蛋白的水平。总之，我们的数据发现，定位于中心体和微管的Nogo - A正向调节Neuro2A细胞系的神经元分化和轴突生长，这表明亚细胞Nogo - A在神经元发育中起着重要作用。
