Cargando…

RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy

RAB39B is located on the X chromosome and encodes the RAB39B protein that belongs to the RAB family. Mutations in RAB39B are known to be associated with X-linked intellectual disability (XLID), Parkinson’s disease, and autism. However, the patho/physiological functions of RAB39B remain largely unkno...

Descripción completa

Detalles Bibliográficos
Autores principales: Niu, Mengxi, Zheng, Naizhen, Wang, Zijie, Gao, Yue, Luo, Xianghua, Chen, Zhicai, Fu, Xing, Wang, Yanyan, Wang, Ting, Liu, Manqing, Yao, Tingting, Yao, Peijie, Meng, Jian, Zhou, Yunqiang, Ge, Yunlong, Wang, Zhanxiang, Ma, Qilin, Xu, Huaxi, Zhang, Yun-wu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753041/
https://www.ncbi.nlm.nih.gov/pubmed/33364235
http://dx.doi.org/10.3389/fcell.2020.598622
_version_ 1783625985661337600
author Niu, Mengxi
Zheng, Naizhen
Wang, Zijie
Gao, Yue
Luo, Xianghua
Chen, Zhicai
Fu, Xing
Wang, Yanyan
Wang, Ting
Liu, Manqing
Yao, Tingting
Yao, Peijie
Meng, Jian
Zhou, Yunqiang
Ge, Yunlong
Wang, Zhanxiang
Ma, Qilin
Xu, Huaxi
Zhang, Yun-wu
author_facet Niu, Mengxi
Zheng, Naizhen
Wang, Zijie
Gao, Yue
Luo, Xianghua
Chen, Zhicai
Fu, Xing
Wang, Yanyan
Wang, Ting
Liu, Manqing
Yao, Tingting
Yao, Peijie
Meng, Jian
Zhou, Yunqiang
Ge, Yunlong
Wang, Zhanxiang
Ma, Qilin
Xu, Huaxi
Zhang, Yun-wu
author_sort Niu, Mengxi
collection PubMed
description RAB39B is located on the X chromosome and encodes the RAB39B protein that belongs to the RAB family. Mutations in RAB39B are known to be associated with X-linked intellectual disability (XLID), Parkinson’s disease, and autism. However, the patho/physiological functions of RAB39B remain largely unknown. In the present study, we established Rab39b knockout (KO) mice, which exhibited overall normal birth rate and morphologies as wild type mice. However, Rab39b deficiency led to reduced anxiety and impaired learning and memory in 2 months old mice. Deletion of Rab39b resulted in impairments of synaptic structures and functions, with reductions in NMDA receptors in the postsynaptic density (PSD). RAB39B deficiency also compromised autophagic flux at basal level, which could be overridden by rapamycin-induced autophagy activation. Further, treatment with rapamycin partially rescued impaired memory and synaptic plasticity in Rab39b KO mice, without affecting the PSD distribution of NMDA receptors. Together, these results suggest that RAB39B plays an important role in regulating both autophagy and synapse formation, and that targeting autophagy may have potential for treating XLID caused by RAB39B loss-of-function mutations.
format Online
Article
Text
id pubmed-7753041
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-77530412020-12-23 RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy Niu, Mengxi Zheng, Naizhen Wang, Zijie Gao, Yue Luo, Xianghua Chen, Zhicai Fu, Xing Wang, Yanyan Wang, Ting Liu, Manqing Yao, Tingting Yao, Peijie Meng, Jian Zhou, Yunqiang Ge, Yunlong Wang, Zhanxiang Ma, Qilin Xu, Huaxi Zhang, Yun-wu Front Cell Dev Biol Cell and Developmental Biology RAB39B is located on the X chromosome and encodes the RAB39B protein that belongs to the RAB family. Mutations in RAB39B are known to be associated with X-linked intellectual disability (XLID), Parkinson’s disease, and autism. However, the patho/physiological functions of RAB39B remain largely unknown. In the present study, we established Rab39b knockout (KO) mice, which exhibited overall normal birth rate and morphologies as wild type mice. However, Rab39b deficiency led to reduced anxiety and impaired learning and memory in 2 months old mice. Deletion of Rab39b resulted in impairments of synaptic structures and functions, with reductions in NMDA receptors in the postsynaptic density (PSD). RAB39B deficiency also compromised autophagic flux at basal level, which could be overridden by rapamycin-induced autophagy activation. Further, treatment with rapamycin partially rescued impaired memory and synaptic plasticity in Rab39b KO mice, without affecting the PSD distribution of NMDA receptors. Together, these results suggest that RAB39B plays an important role in regulating both autophagy and synapse formation, and that targeting autophagy may have potential for treating XLID caused by RAB39B loss-of-function mutations. Frontiers Media S.A. 2020-12-08 /pmc/articles/PMC7753041/ /pubmed/33364235 http://dx.doi.org/10.3389/fcell.2020.598622 Text en Copyright © 2020 Niu, Zheng, Wang, Gao, Luo, Chen, Fu, Wang, Wang, Liu, Yao, Yao, Meng, Zhou, Ge, Wang, Ma, Xu and Zhang. 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 Cell and Developmental Biology
Niu, Mengxi
Zheng, Naizhen
Wang, Zijie
Gao, Yue
Luo, Xianghua
Chen, Zhicai
Fu, Xing
Wang, Yanyan
Wang, Ting
Liu, Manqing
Yao, Tingting
Yao, Peijie
Meng, Jian
Zhou, Yunqiang
Ge, Yunlong
Wang, Zhanxiang
Ma, Qilin
Xu, Huaxi
Zhang, Yun-wu
RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy
title RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy
title_full RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy
title_fullStr RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy
title_full_unstemmed RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy
title_short RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy
title_sort rab39b deficiency impairs learning and memory partially through compromising autophagy
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753041/
https://www.ncbi.nlm.nih.gov/pubmed/33364235
http://dx.doi.org/10.3389/fcell.2020.598622
work_keys_str_mv AT niumengxi rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT zhengnaizhen rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT wangzijie rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT gaoyue rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT luoxianghua rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT chenzhicai rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT fuxing rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT wangyanyan rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT wangting rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT liumanqing rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT yaotingting rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT yaopeijie rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT mengjian rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT zhouyunqiang rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT geyunlong rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT wangzhanxiang rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT maqilin rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT xuhuaxi rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy
AT zhangyunwu rab39bdeficiencyimpairslearningandmemorypartiallythroughcompromisingautophagy