NGL-2是轴突分化过程中PAR复合体的新伙伴。
NGL-2 Is a New Partner of PAR Complex in Axon Differentiation.
作者信息
Xu Gang, Wang Rong, Wang Zeyou, Lei Qianqian, Yu Zhibin, Liu Changhong, Li Peiyao, Yang Zengjie, Cheng Xiping, Li Guiyuan, Wu Minghua
机构信息
Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, and School of Basic Medical Science, Cancer Research Institute, Central South University, Changsha 410078, Hunan, People's Republic of China, Medical College, University of South China, Hengyang 421001, Hunan, People's Republic of China.
School of Basic Medical Science, Cancer Research Institute, Central South University, Changsha 410078, Hunan, People's Republic of China.
出版信息
J Neurosci. 2015 May 6;35(18):7153-64. doi: 10.1523/JNEUROSCI.4726-14.2015.
Neuronal polarization is pivotal for neural network formation during brain development. Axon differentiation is a hallmark of initial neuronal polarization. Here, we report that the leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2) as a polarity regulator that localizes asymmetrically in rat hippocampal neurons and is required for differentiation of the future axon. NGL-2 was associated with PAR complex, and this interaction resulted in local stabilization of axonal microtubules. Further study showed that the C terminal of NGL-2 binds to the PDZ domain of PAR6, and NGL-2 interacts with PAR3 and atypical PKCζ (aPKCζ), with PAR6 acting as a bridge or modifier. Then, NGL-2 regulates the local stabilization of microtubules and promotes axon differentiation by the aPKCζ/microtubule affinity-regulating kinase 2 pathway. These findings reveal the critical role of NGL-2 in regulating axon differentiation in rat hippocampal neurons and reveal a novel partner of the PAR complex.
神经元极化对于大脑发育过程中神经网络的形成至关重要。轴突分化是初始神经元极化的一个标志。在此，我们报告富含亮氨酸重复序列的蛋白网蛋白-G配体-2（NGL-2）作为一种极性调节因子，它不对称地定位于大鼠海马神经元中，并且是未来轴突分化所必需的。NGL-2与PAR复合物相关联，这种相互作用导致轴突微管的局部稳定。进一步研究表明，NGL-2的C末端与PAR6的PDZ结构域结合，并且NGL-2与PAR3和非典型蛋白激酶Cζ（aPKCζ）相互作用，其中PAR6充当桥梁或调节剂。然后，NGL-2通过aPKCζ/微管亲和力调节激酶2途径调节微管的局部稳定并促进轴突分化。这些发现揭示了NGL-2在调节大鼠海马神经元轴突分化中的关键作用，并揭示了PAR复合物的一个新伙伴。
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