Neuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin Paralogs
DYT1 dystonia is a neurodevelopmental disease that manifests during a discrete period of childhood. The disease is caused by impaired function of torsinA, a protein linked to nuclear membrane budding. The relationship of NE budding to neural development and CNS function is unclear, however, obscurin...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716311111 |
| _version_ | 1818914115453714432 |
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| author | Lauren M. Tanabe Chun-Chi Liang William T. Dauer |
| author_facet | Lauren M. Tanabe Chun-Chi Liang William T. Dauer |
| author_sort | Lauren M. Tanabe |
| collection | DOAJ |
| description | DYT1 dystonia is a neurodevelopmental disease that manifests during a discrete period of childhood. The disease is caused by impaired function of torsinA, a protein linked to nuclear membrane budding. The relationship of NE budding to neural development and CNS function is unclear, however, obscuring its potential role in dystonia pathogenesis. We find NE budding begins and resolves during a discrete neurodevelopmental window in torsinA null neurons in vivo. The developmental resolution of NE budding corresponds to increased torsinB protein, while ablating torsinB from torsinA null neurons prevents budding resolution and causes lethal neural dysfunction. Developmental changes in torsinB also correlate with NE bud formation in differentiating DYT1 embryonic stem cells, and overexpression of torsinA or torsinB rescues NE bud formation in this system. These findings identify a torsinA neurodevelopmental window that is essential for normal CNS function and have important implications for dystonia pathogenesis and therapeutics. |
| first_indexed | 2024-12-19T23:41:15Z |
| format | Article |
| id | doaj.art-72be2ee73322494bb080226efeea8e61 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-19T23:41:15Z |
| publishDate | 2016-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-72be2ee73322494bb080226efeea8e612022-12-21T20:01:25ZengElsevierCell Reports2211-12472016-09-0116123322333310.1016/j.celrep.2016.08.044Neuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin ParalogsLauren M. Tanabe0Chun-Chi Liang1William T. Dauer2Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USADepartment of Neurology, University of Michigan, Ann Arbor, MI 48109, USADepartment of Neurology, University of Michigan, Ann Arbor, MI 48109, USADYT1 dystonia is a neurodevelopmental disease that manifests during a discrete period of childhood. The disease is caused by impaired function of torsinA, a protein linked to nuclear membrane budding. The relationship of NE budding to neural development and CNS function is unclear, however, obscuring its potential role in dystonia pathogenesis. We find NE budding begins and resolves during a discrete neurodevelopmental window in torsinA null neurons in vivo. The developmental resolution of NE budding corresponds to increased torsinB protein, while ablating torsinB from torsinA null neurons prevents budding resolution and causes lethal neural dysfunction. Developmental changes in torsinB also correlate with NE bud formation in differentiating DYT1 embryonic stem cells, and overexpression of torsinA or torsinB rescues NE bud formation in this system. These findings identify a torsinA neurodevelopmental window that is essential for normal CNS function and have important implications for dystonia pathogenesis and therapeutics.http://www.sciencedirect.com/science/article/pii/S2211124716311111 |
| spellingShingle | Lauren M. Tanabe Chun-Chi Liang William T. Dauer Neuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin Paralogs Cell Reports |
| title | Neuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin Paralogs |
| title_full | Neuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin Paralogs |
| title_fullStr | Neuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin Paralogs |
| title_full_unstemmed | Neuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin Paralogs |
| title_short | Neuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin Paralogs |
| title_sort | neuronal nuclear membrane budding occurs during a developmental window modulated by torsin paralogs |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716311111 |
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