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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00518

Neuroligin 3 regulates dendritic outgrowth by modulating Akt/mTOR signaling

Jing Xu1, Yong-lan Du1, Jing-wei Xu1, Xiao-ge Hu2, Lin-fan Gu3, Xiu-mao Li4, Ping-hong Hu1, Tai-lin Liao1, Qiang-qiang Xia1, Qi Sun1,  Lei Shi5,  Jianhong Luo1,  Jun Xia6,  Ziyi Wang6* and  Junyu Xu1*
  • 1Zhejiang University, China
  • 2Hangzhou First People's Hospital, China
  • 3Zhejiang University-University of Edinburgh Institute, China
  • 4Second Affiliated Hospital, School of Medicine, Zhejiang University, China
  • 5Jinan University, China
  • 6Hong Kong University of Science and Technology, Hong Kong

Neuroligins (NLs) are a group of postsynaptic cell adhesion molecules function in synaptogenesis and synaptic transmission. Genetic defects in NL3, a member of the NL protein family, are associated with autism. Studies in rodents have found that mutations of NL3 gene lead to increased growth and complexity in dendrites in the central nervous system. However, the detailed mechanism is still unclear. In our study, we found that deficiency of NL3 led to morphological changes of the pyramidal neurons in layer II/III somatosensory cortex in mice, including enlarged somata, elongated dendritic length, and increased dendritic complexity. Knockdown of NL3 in cultured rat neurons upregulated Akt/mTOR signaling, resulting in both increased protein synthesis and dendritic growth. Treating neurons with either rapamycin to inhibit the mTOR or LY294002 to inhibit the PI3K/Akt activity rescued the morphological abnormalities resulting from either NL3 knockdown or knockout. In addition, we found that the hyperactivated Akt/mTOR signaling associated with NL3 defects was mediated by a reduction in PTEN expression, and that MAGI-2, a scaffold protein, interacted with both NL3 and PTEN and could be a linker between NL3 and Akt/mTOR signaling pathway. In conclusion, our results suggest that NL3 regulates neuronal morphology, especially dendritic outgrowth, by modulating the PTEN/Akt/mTOR signaling pathway, probably via MAGI-2. Thereby, this study provides a new link between NL3 and neuronal morphology.

Keywords: Neuroligin 3, AKT/mTOR, Pten, MAGI-2, Dendritic outgrowth

Received: 17 Jul 2019; Accepted: 04 Nov 2019.

Copyright: © 2019 Xu, Du, Xu, Hu, Gu, Li, Hu, Liao, Xia, Sun, Shi, Luo, Xia, Wang and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Ziyi Wang, Hong Kong University of Science and Technology, Kowloon, Hong Kong, mtray@qq.com
Mx. Junyu Xu, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China, junyu@zju.edu.cn