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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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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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 |
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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 |
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