Cargando…
MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome
The methyl-CpG-binding protein 2 (MeCP2) gene, MECP2, is an X-linked gene encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrome (RTT). However, the molecular mechanism of MECP2-mutation-caused RTT is less known. Here we find that MeCP2 could be SUMO-modified by the E3 ligase PIAS1 a...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4743023/ https://www.ncbi.nlm.nih.gov/pubmed/26842955 http://dx.doi.org/10.1038/ncomms10552 |
_version_ | 1782414290395856896 |
---|---|
author | Tai, Derek J. C. Liu, Yen C. Hsu, Wei L. Ma, Yun L. Cheng, Sin J. Liu, Shau Y. Lee, Eminy H. Y. |
author_facet | Tai, Derek J. C. Liu, Yen C. Hsu, Wei L. Ma, Yun L. Cheng, Sin J. Liu, Shau Y. Lee, Eminy H. Y. |
author_sort | Tai, Derek J. C. |
collection | PubMed |
description | The methyl-CpG-binding protein 2 (MeCP2) gene, MECP2, is an X-linked gene encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrome (RTT). However, the molecular mechanism of MECP2-mutation-caused RTT is less known. Here we find that MeCP2 could be SUMO-modified by the E3 ligase PIAS1 at Lys-412. MeCP2 phosphorylation (at Ser-421 and Thr-308) facilitates MeCP2 SUMOylation, and MeCP2 SUMOylation is induced by NMDA, IGF-1 and CRF in the rat brain. MeCP2 SUMOylation releases CREB from the repressor complex and enhances Bdnf mRNA expression. Several MECP2 mutations identified in RTT patients show decreased MeCP2 SUMOylation. Re-expression of wild-type MeCP2 or SUMO-modified MeCP2 in Mecp2-null neurons rescues the deficits of social interaction, fear memory and LTP observed in Mecp2 conditional knockout (cKO) mice. These results together reveal an important role of MeCP2 SUMOylation in social interaction, memory and synaptic plasticity, and that abnormal MeCP2 SUMOylation is implicated in RTT. |
format | Online Article Text |
id | pubmed-4743023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47430232016-03-04 MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome Tai, Derek J. C. Liu, Yen C. Hsu, Wei L. Ma, Yun L. Cheng, Sin J. Liu, Shau Y. Lee, Eminy H. Y. Nat Commun Article The methyl-CpG-binding protein 2 (MeCP2) gene, MECP2, is an X-linked gene encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrome (RTT). However, the molecular mechanism of MECP2-mutation-caused RTT is less known. Here we find that MeCP2 could be SUMO-modified by the E3 ligase PIAS1 at Lys-412. MeCP2 phosphorylation (at Ser-421 and Thr-308) facilitates MeCP2 SUMOylation, and MeCP2 SUMOylation is induced by NMDA, IGF-1 and CRF in the rat brain. MeCP2 SUMOylation releases CREB from the repressor complex and enhances Bdnf mRNA expression. Several MECP2 mutations identified in RTT patients show decreased MeCP2 SUMOylation. Re-expression of wild-type MeCP2 or SUMO-modified MeCP2 in Mecp2-null neurons rescues the deficits of social interaction, fear memory and LTP observed in Mecp2 conditional knockout (cKO) mice. These results together reveal an important role of MeCP2 SUMOylation in social interaction, memory and synaptic plasticity, and that abnormal MeCP2 SUMOylation is implicated in RTT. Nature Publishing Group 2016-02-04 /pmc/articles/PMC4743023/ /pubmed/26842955 http://dx.doi.org/10.1038/ncomms10552 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Tai, Derek J. C. Liu, Yen C. Hsu, Wei L. Ma, Yun L. Cheng, Sin J. Liu, Shau Y. Lee, Eminy H. Y. MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome |
title | MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome |
title_full | MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome |
title_fullStr | MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome |
title_full_unstemmed | MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome |
title_short | MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome |
title_sort | mecp2 sumoylation rescues mecp2-mutant-induced behavioural deficits in a mouse model of rett syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4743023/ https://www.ncbi.nlm.nih.gov/pubmed/26842955 http://dx.doi.org/10.1038/ncomms10552 |
work_keys_str_mv | AT taiderekjc mecp2sumoylationrescuesmecp2mutantinducedbehaviouraldeficitsinamousemodelofrettsyndrome AT liuyenc mecp2sumoylationrescuesmecp2mutantinducedbehaviouraldeficitsinamousemodelofrettsyndrome AT hsuweil mecp2sumoylationrescuesmecp2mutantinducedbehaviouraldeficitsinamousemodelofrettsyndrome AT mayunl mecp2sumoylationrescuesmecp2mutantinducedbehaviouraldeficitsinamousemodelofrettsyndrome AT chengsinj mecp2sumoylationrescuesmecp2mutantinducedbehaviouraldeficitsinamousemodelofrettsyndrome AT liushauy mecp2sumoylationrescuesmecp2mutantinducedbehaviouraldeficitsinamousemodelofrettsyndrome AT leeeminyhy mecp2sumoylationrescuesmecp2mutantinducedbehaviouraldeficitsinamousemodelofrettsyndrome |