Format

Send to

Choose Destination
Sci Rep. 2017 Jul 7;7(1):4912. doi: 10.1038/s41598-017-05239-7.

PKCα-mediated phosphorylation of LSD1 is required for presynaptic plasticity and hippocampal learning and memory.

Author information

1
Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, Korea.
2
Laboratory of Molecular and Cellular Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, Korea.
3
Department of Physiology, Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Korea.
4
Department of Life and Nanopharmaceutical Sciences, Department of Maxillofacial Biomedical Engineering, School of Dentistry, Kyung Hee University, Seoul, 02447, Korea.
5
Laboratory of Molecular and Cellular Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, Korea. sbaek@snu.ac.kr.
6
Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, Korea. kaang@snu.ac.kr.

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.

PMID:
28687800
PMCID:
PMC5501860
DOI:
10.1038/s41598-017-05239-7
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center