KCTD10 regulates brain development by destabilizing brain disorder-associated protein KCTD13
KCTD10 belongs to the KCTD (potassiumchannel tetramerization domain) family, many members of which are associated with neuropsychiatric disorders. However, the biological function underlying the association with brain disorders remains to be explored. Here, we reveal that Kctd10 is highly expressed in neuronal progenitors and layer V neurons throughout brain development. Kctd10 deficiency triggers abnormal proliferation and differentiation of neuronal progenitors, reduced deep-layer (especially layer V) neurons, increased upper-layer neurons, and lowered brain size. Mechanistically, we screened and identified a unique KCTD10-interacting protein, KCTD13, associated with neurodevelopmental disorders. KCTD10 mediated the ubiquitination-dependent degradation of KCTD13 and KCTD10 ablation resulted in a considerable increase of KCTD13 expression in the developing cortex. KCTD13 overexpression in neuronal progenitors led to reduced proliferation and abnormal cell distribution, mirroring KCTD10 deficiency. Notably, mice with brain-specific Kctd10 knockout exhibited obvious motor deficits. This study uncovers the physiological function of KCTD10 and provides unique insights into the pathogenesis of neurodevelopmental disorders.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:121 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 121(2024), 12 vom: 19. März, Seite e2315707121 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cheng, Jianbo [VerfasserIn] |
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| Links: |
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| Themen: |
Cortical neurogenesis |
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| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 27.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2315707121 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369790723 |
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| 100 | 1 | |a Cheng, Jianbo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a KCTD10 regulates brain development by destabilizing brain disorder-associated protein KCTD13 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a KCTD10 belongs to the KCTD (potassiumchannel tetramerization domain) family, many members of which are associated with neuropsychiatric disorders. However, the biological function underlying the association with brain disorders remains to be explored. Here, we reveal that Kctd10 is highly expressed in neuronal progenitors and layer V neurons throughout brain development. Kctd10 deficiency triggers abnormal proliferation and differentiation of neuronal progenitors, reduced deep-layer (especially layer V) neurons, increased upper-layer neurons, and lowered brain size. Mechanistically, we screened and identified a unique KCTD10-interacting protein, KCTD13, associated with neurodevelopmental disorders. KCTD10 mediated the ubiquitination-dependent degradation of KCTD13 and KCTD10 ablation resulted in a considerable increase of KCTD13 expression in the developing cortex. KCTD13 overexpression in neuronal progenitors led to reduced proliferation and abnormal cell distribution, mirroring KCTD10 deficiency. Notably, mice with brain-specific Kctd10 knockout exhibited obvious motor deficits. This study uncovers the physiological function of KCTD10 and provides unique insights into the pathogenesis of neurodevelopmental disorders | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a KCTD10 | |
| 650 | 4 | |a KCTD13 | |
| 650 | 4 | |a cortical neurogenesis | |
| 650 | 4 | |a motor deficits | |
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| 700 | 1 | |a Wang, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Manpei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Guozhong |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Senwei |e verfasserin |4 aut | |
| 700 | 1 | |a Mu, Chenjun |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Mengyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Xiangbin |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Yangxuan |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jiada |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Kun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Faxiang |e verfasserin |4 aut | |
| 700 | 1 | |a Duan, Ranhui |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Zhiheng |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Ling |e verfasserin |4 aut | |
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