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RNF216 Regulates the Migration of Immortalized GnRH Neurons by Suppressing Beclin1-Mediated Autophagy

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 GN1...

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Autores principales: Li, Fangfang, Li, Dengfeng, Liu, Huadie, Cao, Bei-Bei, Jiang, Fang, Chen, Dan-Na, Li, Jia-Da
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354547/
https://www.ncbi.nlm.nih.gov/pubmed/30733708
http://dx.doi.org/10.3389/fendo.2019.00012
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author Li, Fangfang
Li, Dengfeng
Liu, Huadie
Cao, Bei-Bei
Jiang, Fang
Chen, Dan-Na
Li, Jia-Da
author_facet Li, Fangfang
Li, Dengfeng
Liu, Huadie
Cao, Bei-Bei
Jiang, Fang
Chen, Dan-Na
Li, Jia-Da
author_sort Li, Fangfang
collection PubMed
description 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.
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spelling pubmed-63545472019-02-07 RNF216 Regulates the Migration of Immortalized GnRH Neurons by Suppressing Beclin1-Mediated Autophagy Li, Fangfang Li, Dengfeng Liu, Huadie Cao, Bei-Bei Jiang, Fang Chen, Dan-Na Li, Jia-Da Front Endocrinol (Lausanne) Endocrinology 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. Frontiers Media S.A. 2019-01-24 /pmc/articles/PMC6354547/ /pubmed/30733708 http://dx.doi.org/10.3389/fendo.2019.00012 Text en Copyright © 2019 Li, Li, Liu, Cao, Jiang, Chen and Li. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Endocrinology
Li, Fangfang
Li, Dengfeng
Liu, Huadie
Cao, Bei-Bei
Jiang, Fang
Chen, Dan-Na
Li, Jia-Da
RNF216 Regulates the Migration of Immortalized GnRH Neurons by Suppressing Beclin1-Mediated Autophagy
title RNF216 Regulates the Migration of Immortalized GnRH Neurons by Suppressing Beclin1-Mediated Autophagy
title_full RNF216 Regulates the Migration of Immortalized GnRH Neurons by Suppressing Beclin1-Mediated Autophagy
title_fullStr RNF216 Regulates the Migration of Immortalized GnRH Neurons by Suppressing Beclin1-Mediated Autophagy
title_full_unstemmed RNF216 Regulates the Migration of Immortalized GnRH Neurons by Suppressing Beclin1-Mediated Autophagy
title_short RNF216 Regulates the Migration of Immortalized GnRH Neurons by Suppressing Beclin1-Mediated Autophagy
title_sort rnf216 regulates the migration of immortalized gnrh neurons by suppressing beclin1-mediated autophagy
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354547/
https://www.ncbi.nlm.nih.gov/pubmed/30733708
http://dx.doi.org/10.3389/fendo.2019.00012
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