Neuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin Paralogs
| Autor: | William T. Dauer, Lauren M. Tanabe, Chun Chi Liang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Nuclear Envelope Neurogenesis Period (gene) Biology Article General Biochemistry Genetics and Molecular Biology Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Nuclear membrane lcsh:QH301-705.5 Neurons Genetics Dystonia Budding Membrane budding medicine.disease Embryonic stem cell Cell biology 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Neurodevelopmental Disorders Mutation Neural development 030217 neurology & neurosurgery Molecular Chaperones |
| Zdroj: | Cell Reports, Vol 16, Iss 12, Pp 3322-3333 (2016) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2016.08.044 |
| Popis: | SummaryDYT1 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. |
| Databáze: | OpenAIRE |
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