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

Front. Endocrinol. | doi: 10.3389/fendo.2019.00012

RNF216 regulates the migration of immortalized GnRH neurons by suppressing Beclin1-mediated autophagy

 Dengfeng Li1, Fangfang Li1, Huadie Liu1, Beibei Cao1, Fang Jiang1 and  Jiada Li1*
  • 1Central South University, China

RNF216, encoding an E3 ubiquitin ligase, has been identified as a causative gene for Gordon Holmes syndrome, characterized by ataxia, dementia and hypogonadotropic hypogonadism. However, it is still elusive how deficiency in RNF216 leads to hypogonadotropic hypogonadism. In this study, by using GN11 immature GnRH neuronal cell line, we demonstrated an important role of RNF216 in the GnRH neuron migration. RNA interference of RNF216 inhibited GN11 cell migration, but had no effect on the proliferation of GN11 cells or GnRH expression. Knockdown of RNF216 increased the protein levels of its targets, Arc and Beclin1. RNAi of Beclin1, but not Arc, normalized the suppressive effect caused by RNF216 knockdown. As Beclin1 plays a critical role in the autophagy regulation, we further demonstrated that RNAi of RNF216 led to increase in autophagy, and autophagy inhibitor CQ and 3-MA rescued the GN11 cell migration deficit caused by RNF216 knockdown. We further demonstrated that pharmacological increase autophagy by rapamycin could suppress the GN11 cell migration. We thus have identified that RNF216 regulates the migration of GnRH neuron by suppressing Beclin1 mediated autophagy, and indicated a potential contribution of autophagy to the hypogonadotropic hypogonadism.

Keywords: hypogonadotropic hypogonadism, GnRH neuron, RNF216, Migration, Autophagy

Received: 05 Oct 2018; Accepted: 10 Jan 2019.

Edited by:

T John Wu, Uniformed Services University of the Health Sciences, United States

Reviewed by:

Wilson C. Chung, Kent State University, United States
Darwin O. Larco, Affinivax, Inc, United States  

Copyright: © 2019 Li, Li, Liu, Cao, Jiang and Li. 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: Prof. Jiada Li, Central South University, Changsha, China, lijiada@sklmg.edu.cn