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

Lauren M. Tanabe, Chun Chi Liang, William T. Dauer

Research output: Contribution to journalArticle

20 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)3322-3333
Number of pages12
JournalCell Reports
Volume16
Issue number12
DOIs
Publication statusPublished - Sep 20 2016
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this