Neuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin Paralogs.

ABSTRACT: 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

SUBMITTER: Tanabe LM 

PROVIDER: S-EPMC5061049 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature