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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. Copyright © 2015 the authors 0270-6474/15/357153-12$15.00/0.

Citation

Gang Xu, Rong Wang, Zeyou Wang, Qianqian Lei, Zhibin Yu, Changhong Liu, Peiyao Li, Zengjie Yang, Xiping Cheng, Guiyuan Li, Minghua Wu. NGL-2 Is a New Partner of PAR Complex in Axon Differentiation. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2015 May 6;35(18):7153-64

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PMID: 25948265

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