Atai, Nadia A.Ryan, Scott D.Kothary, RashmiBreakefield, XandraNery, Flávia C.2013-03-082012Atai, Nadia A., Scott D. Ryan, Rashmi Kothary, Xandra O. Breakefield, and Flávia C. Nery. 2012. Untethering the nuclear envelope and cytoskeleton: Biologically distinct dystonias arising from a common cellular dysfunction. International Journal of Cell Biology 2012:634214.1687-8876http://nrs.harvard.edu/urn-3:HUL.InstRepos:10382936Most cases of early onset DYT1 dystonia in humans are caused by a GAG deletion in the TOR1A gene leading to loss of a glutamic acid (\(\Delta\)E) in the torsinA protein, which underlies a movement disorder associated with neuronal dysfunction without apparent neurodegeneration. Mutation/deletion of the gene (Dst) encoding dystonin in mice results in a dystonic movement disorder termed dystonia musculorum, which resembles aspects of dystonia in humans. While torsinA and dystonin proteins do not share modular domain architecture, they participate in a similar function by modulating a structural link between the nuclear envelope and the cytoskeleton in neuronal cells. We suggest that through a shared interaction with the nuclear envelope protein nesprin-3\(\alpha\), torsinA and the neuronal dystonin-a2 isoform comprise a bridge complex between the outer nuclear membrane and the cytoskeleton, which is critical for some aspects of neuronal development and function. Elucidation of the overlapping roles of torsinA and dystonin-a2 in nuclear/endoplasmic reticulum dynamics should provide insights into the cellular mechanisms underlying the dystonic phenotype.en-USJournal Article2013-03-0810.1155/2012/634214