Familial, early onset, generalized torsion dystonia is the most common and severe primary dystonia. The majority of cases are caused by a 3-bp deletion (GAG) in the coding region of the DYT1 (TOR1A) gene. The cellular and regional distribution of torsinA protein, which is restricted to neuronal cells and present in all brain regions by the age of 2 months has been described recently in human developing brain. TorsinB is a member of the same family of proteins and is highly homologous with its gene adjacent to that for torsinA on chromosome 9q34. TorsinA and torsinB share several remarkable features suggesting that they may interact in vivo. This study examined the expression of torsinB in the human brain of fetuses, infants and children up to 7 years of age. Our results indicate that torsinB protein expression is temporarily and spatially regulated in a similar fashion as torsinA. Expression of torsinB protein was detectable beginning at four to 8 weeks of age in the cerebellum (Purkinje cells), substantia nigra (dopaminergic neurons), hippocampus and basal ganglia and was predominantly restricted to neuronal cells. In contrast to torsinA, torsinB immunoreactivity was found more readily in the nuclear envelope. High levels of torsinB protein were maintained throughout infancy, childhood and adulthood suggesting that torsinB is also needed for developmental events occurring in the early postnatal phase and is necessary for functional activity throughout life.
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TorsinB overexpression prevents abnormal twisting in DYT1 dystonia mouse models.
Elife
March 2020
Department of Neurology, University of Michigan, Ann Arbor, United States.
Genetic redundancy can be exploited to identify therapeutic targets for inherited disorders. We explored this possibility in DYT1 dystonia, a neurodevelopmental movement disorder caused by a loss-of-function (LOF) mutation in the gene encoding torsinA. Prior work demonstrates that torsinA and its paralog torsinB have conserved functions at the nuclear envelope.
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View Article and Find Full Text PDFNeuronal Nuclear Membrane Budding Occurs during a Developmental Window Modulated by Torsin Paralogs.
Cell Rep
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Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
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.
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April 2016
From the Departments of Molecular Biophysics and Biochemistry and Cell Biology, Yale University, New Haven, Connecticut 06520 and
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August 2015
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA
Article Synopsis
- * TorsinA and TorsinB are ATPases involved in nuclear envelope dynamics and the herpes simplex virus 1 (HSV-1) nuclear egress, relying on co-factors LAP1 and LULL1 for their function.
- * Researchers employed CRISPR/Cas9 to create single and double knockout cell lines to study the impact of these proteins on HSV-1 production, finding that LULL1 is a crucial activator, significantly affecting viral growth.
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