1. NGL-2 Is a New Partner of PAR Complex in Axon Differentiation
- Author
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Qianqian Lei, Rong Wang, Xiping Cheng, Minghua Wu, Zeyou Wang, Gang Xu, Zeng-Jie Yang, Guiyuan Li, Changhong Liu, Zhibin Yu, and Peiyao Li
- Subjects
Male ,PDZ domain ,Regulator ,Nerve Tissue Proteins ,Biology ,Hippocampal formation ,GPI-Linked Proteins ,Axon hillock ,Hippocampus ,Microtubule ,Netrin ,medicine ,Animals ,Humans ,Axon ,Cells, Cultured ,Adaptor Proteins, Signal Transducing ,Kinase ,General Neuroscience ,Cell Differentiation ,Articles ,Axons ,Rats ,Cell biology ,HEK293 Cells ,medicine.anatomical_structure ,nervous system ,Female ,Netrins ,Carrier Proteins ,Neuroscience - Abstract
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.
- Published
- 2015