Activator of KAT3 histone acetyltransferase family ameliorates a neurodevelopmental disorder phenotype in the syntaxin 1A ablated mouse model
Summary: Syntaxin-1A (stx1a) repression causes a neurodevelopmental disorder phenotype, low latent inhibition (LI) behavior, by disrupting 5-hydroxytryptaminergic (5-HTergic) systems. Herein, we discovered that lysine acetyltransferase (KAT) 3B increases stx1a neuronal transcription and TTK21, a KAT...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724004297 |
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| author | Takahiro Nakayama Akash K. Singh Toshiyuki Fukutomi Noriyuki Uchida Yasuo Terao Hiroki Hamada Takahiro Muraoka Eswaramoorthy Muthusamy Tapas K. Kundu Kimio Akagawa |
| author_facet | Takahiro Nakayama Akash K. Singh Toshiyuki Fukutomi Noriyuki Uchida Yasuo Terao Hiroki Hamada Takahiro Muraoka Eswaramoorthy Muthusamy Tapas K. Kundu Kimio Akagawa |
| author_sort | Takahiro Nakayama |
| collection | DOAJ |
| description | Summary: Syntaxin-1A (stx1a) repression causes a neurodevelopmental disorder phenotype, low latent inhibition (LI) behavior, by disrupting 5-hydroxytryptaminergic (5-HTergic) systems. Herein, we discovered that lysine acetyltransferase (KAT) 3B increases stx1a neuronal transcription and TTK21, a KAT3 activator, induces stx1a transcription and 5-HT release in vitro. Furthermore, glucose-derived CSP-TTK21 could restore decreased stx1a expression, 5-HTergic systems in the brain, and low LI in stx1a (+/−) mice by crossing the blood-brain barrier, whereas the KAT3 inhibitor suppresses stx1a expression, 5-HTergic systems, and LI behaviors in wild-type mice. Finally, in wild-type and stx1a (−/−) mice treated with IKK inhibitors and CSP-TTK21, respectively, we show that KAT3 activator-induced LI improvement is a direct consequence of KAT3B-stx1a pathway, not a side effect. In conclusion, KAT3B can positively regulate stx1a transcription in neurons, and increasing neuronal stx1a expression and 5-HTergic systems by a KAT3 activator consequently improves the low LI behavior in the stx1a ablation mouse model. |
| first_indexed | 2024-04-24T10:04:14Z |
| format | Article |
| id | doaj.art-7082df1e29b6458ba0cf338791935a20 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-24T10:04:14Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7082df1e29b6458ba0cf338791935a202024-04-13T04:21:14ZengElsevierCell Reports2211-12472024-04-01434114101Activator of KAT3 histone acetyltransferase family ameliorates a neurodevelopmental disorder phenotype in the syntaxin 1A ablated mouse modelTakahiro Nakayama0Akash K. Singh1Toshiyuki Fukutomi2Noriyuki Uchida3Yasuo Terao4Hiroki Hamada5Takahiro Muraoka6Eswaramoorthy Muthusamy7Tapas K. Kundu8Kimio Akagawa9Department of Medical Physiology, Kyorin University School of Medicine, Tokyo 181-8611, Japan; Corresponding authorTranscription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India; Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, IndiaDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611, JapanDepartment of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Tokyo 184-8588, JapanDepartment of Medical Physiology, Kyorin University School of Medicine, Tokyo 181-8611, JapanDepartment of Life Science, Okayama University of Science, Okayama 700-0005, JapanDepartment of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Tokyo 184-8588, JapanChemistry and Physics of Materials Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, IndiaTranscription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India; Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, IndiaDepartment of Medical Physiology, Kyorin University School of Medicine, Tokyo 181-8611, JapanSummary: Syntaxin-1A (stx1a) repression causes a neurodevelopmental disorder phenotype, low latent inhibition (LI) behavior, by disrupting 5-hydroxytryptaminergic (5-HTergic) systems. Herein, we discovered that lysine acetyltransferase (KAT) 3B increases stx1a neuronal transcription and TTK21, a KAT3 activator, induces stx1a transcription and 5-HT release in vitro. Furthermore, glucose-derived CSP-TTK21 could restore decreased stx1a expression, 5-HTergic systems in the brain, and low LI in stx1a (+/−) mice by crossing the blood-brain barrier, whereas the KAT3 inhibitor suppresses stx1a expression, 5-HTergic systems, and LI behaviors in wild-type mice. Finally, in wild-type and stx1a (−/−) mice treated with IKK inhibitors and CSP-TTK21, respectively, we show that KAT3 activator-induced LI improvement is a direct consequence of KAT3B-stx1a pathway, not a side effect. In conclusion, KAT3B can positively regulate stx1a transcription in neurons, and increasing neuronal stx1a expression and 5-HTergic systems by a KAT3 activator consequently improves the low LI behavior in the stx1a ablation mouse model.http://www.sciencedirect.com/science/article/pii/S2211124724004297CP: NeuroscienceCP: Molecular biology |
| spellingShingle | Takahiro Nakayama Akash K. Singh Toshiyuki Fukutomi Noriyuki Uchida Yasuo Terao Hiroki Hamada Takahiro Muraoka Eswaramoorthy Muthusamy Tapas K. Kundu Kimio Akagawa Activator of KAT3 histone acetyltransferase family ameliorates a neurodevelopmental disorder phenotype in the syntaxin 1A ablated mouse model Cell Reports CP: Neuroscience CP: Molecular biology |
| title | Activator of KAT3 histone acetyltransferase family ameliorates a neurodevelopmental disorder phenotype in the syntaxin 1A ablated mouse model |
| title_full | Activator of KAT3 histone acetyltransferase family ameliorates a neurodevelopmental disorder phenotype in the syntaxin 1A ablated mouse model |
| title_fullStr | Activator of KAT3 histone acetyltransferase family ameliorates a neurodevelopmental disorder phenotype in the syntaxin 1A ablated mouse model |
| title_full_unstemmed | Activator of KAT3 histone acetyltransferase family ameliorates a neurodevelopmental disorder phenotype in the syntaxin 1A ablated mouse model |
| title_short | Activator of KAT3 histone acetyltransferase family ameliorates a neurodevelopmental disorder phenotype in the syntaxin 1A ablated mouse model |
| title_sort | activator of kat3 histone acetyltransferase family ameliorates a neurodevelopmental disorder phenotype in the syntaxin 1a ablated mouse model |
| topic | CP: Neuroscience CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724004297 |
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