PKCα-mediated phosphorylation of LSD1 is required for presynaptic plasticity and hippocampal learning and memory
Abstract Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates in transcriptional repression or activation. Recent studies reported that LSD1 is involved in learning and memory. Although LSD1 phosphorylation by PKCα was implicated in circadian rhythmicity, the importance of...
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Nature Portfolio
2017
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oai:doaj.org-article:0d31f3b5d7f647abb2626298419871e92021-12-02T16:07:01ZPKCα-mediated phosphorylation of LSD1 is required for presynaptic plasticity and hippocampal learning and memory10.1038/s41598-017-05239-72045-2322https://doaj.org/article/0d31f3b5d7f647abb2626298419871e92017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05239-7https://doaj.org/toc/2045-2322Abstract Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates in transcriptional repression or activation. Recent studies reported that LSD1 is involved in learning and memory. Although LSD1 phosphorylation by PKCα was implicated in circadian rhythmicity, the importance of LSD1 phosphorylation in learning and memory is unknown. In this study, we examined the roles of LSD1 in synaptic plasticity and memory using Lsd1 SA/SA knock-in (KI) mice, in which a PKCα phosphorylation site is mutated. Interestingly, short-term and long-term contextual fear memory as well as spatial memory were impaired in Lsd1 KI mice. In addition, short-term synaptic plasticity, such as paired pulse ratio and post-tetanic potentiation was impaired, whereas long-term synaptic plasticity, including long-term potentiation and long-term depression, was normal. Moreover, the frequency of miniature excitatory postsynaptic current was significantly increased, suggesting presynaptic dysfunction in Lsd1 KI mice. Consistent with this, RNA-seq analysis using the hippocampus of Lsd1 KI mice showed significant alterations in the expressions of presynaptic function-related genes. Intriguingly, LSD1n-SA mutant showed diminished binding to histone deacetylase 1 (HDAC1) compared to LSD1n-WT in SH-SY5Y cells. These results suggest that LSD1 is involved in the regulation of presynaptic gene expression and subsequently regulates the hippocampus-dependent memory in phosphorylation-dependent manner.Chae-Seok LimHye Jin NamJaehyun LeeDongha KimJa Eun ChoiSukJae Joshua KangSomi KimHyopil KimChuljung KwakKyu-Won ShimSiyong KimHyoung-Gon KoRo Un LeeEun-Hae JangJuyoun YooJaehoon ShimMd Ariful IslamYong-Seok LeeJae-Hyung LeeSung Hee BaekBong-Kiun KaangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017) |
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| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Chae-Seok Lim Hye Jin Nam Jaehyun Lee Dongha Kim Ja Eun Choi SukJae Joshua Kang Somi Kim Hyopil Kim Chuljung Kwak Kyu-Won Shim Siyong Kim Hyoung-Gon Ko Ro Un Lee Eun-Hae Jang Juyoun Yoo Jaehoon Shim Md Ariful Islam Yong-Seok Lee Jae-Hyung Lee Sung Hee Baek Bong-Kiun Kaang PKCα-mediated phosphorylation of LSD1 is required for presynaptic plasticity and hippocampal learning and memory |
| description |
Abstract Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates in transcriptional repression or activation. Recent studies reported that LSD1 is involved in learning and memory. Although LSD1 phosphorylation by PKCα was implicated in circadian rhythmicity, the importance of LSD1 phosphorylation in learning and memory is unknown. In this study, we examined the roles of LSD1 in synaptic plasticity and memory using Lsd1 SA/SA knock-in (KI) mice, in which a PKCα phosphorylation site is mutated. Interestingly, short-term and long-term contextual fear memory as well as spatial memory were impaired in Lsd1 KI mice. In addition, short-term synaptic plasticity, such as paired pulse ratio and post-tetanic potentiation was impaired, whereas long-term synaptic plasticity, including long-term potentiation and long-term depression, was normal. Moreover, the frequency of miniature excitatory postsynaptic current was significantly increased, suggesting presynaptic dysfunction in Lsd1 KI mice. Consistent with this, RNA-seq analysis using the hippocampus of Lsd1 KI mice showed significant alterations in the expressions of presynaptic function-related genes. Intriguingly, LSD1n-SA mutant showed diminished binding to histone deacetylase 1 (HDAC1) compared to LSD1n-WT in SH-SY5Y cells. These results suggest that LSD1 is involved in the regulation of presynaptic gene expression and subsequently regulates the hippocampus-dependent memory in phosphorylation-dependent manner. |
| format |
article |
| author |
Chae-Seok Lim Hye Jin Nam Jaehyun Lee Dongha Kim Ja Eun Choi SukJae Joshua Kang Somi Kim Hyopil Kim Chuljung Kwak Kyu-Won Shim Siyong Kim Hyoung-Gon Ko Ro Un Lee Eun-Hae Jang Juyoun Yoo Jaehoon Shim Md Ariful Islam Yong-Seok Lee Jae-Hyung Lee Sung Hee Baek Bong-Kiun Kaang |
| author_facet |
Chae-Seok Lim Hye Jin Nam Jaehyun Lee Dongha Kim Ja Eun Choi SukJae Joshua Kang Somi Kim Hyopil Kim Chuljung Kwak Kyu-Won Shim Siyong Kim Hyoung-Gon Ko Ro Un Lee Eun-Hae Jang Juyoun Yoo Jaehoon Shim Md Ariful Islam Yong-Seok Lee Jae-Hyung Lee Sung Hee Baek Bong-Kiun Kaang |
| author_sort |
Chae-Seok Lim |
| title |
PKCα-mediated phosphorylation of LSD1 is required for presynaptic plasticity and hippocampal learning and memory |
| title_short |
PKCα-mediated phosphorylation of LSD1 is required for presynaptic plasticity and hippocampal learning and memory |
| title_full |
PKCα-mediated phosphorylation of LSD1 is required for presynaptic plasticity and hippocampal learning and memory |
| title_fullStr |
PKCα-mediated phosphorylation of LSD1 is required for presynaptic plasticity and hippocampal learning and memory |
| title_full_unstemmed |
PKCα-mediated phosphorylation of LSD1 is required for presynaptic plasticity and hippocampal learning and memory |
| title_sort |
pkcα-mediated phosphorylation of lsd1 is required for presynaptic plasticity and hippocampal learning and memory |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/0d31f3b5d7f647abb2626298419871e9 |
| work_keys_str_mv |
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