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Primary torsion dystonia, also known as DYT1, is the most prevalent type of dystonia, a set of neurological movement disorders that affect approximately
330 per million of the population. This autosomal dominant disease has been linked to the dyt1 gene on chromosome 9q34, which encodes the 332 amino
acid protein torsinA. Most genetically inherited cases of DYT1 have been linked to a GAG deletion that results in the loss of one glutamic acid from a pair
in a highly conserved region near the C-terminus of torsinA. Recent research has shown that wild-type torsinA is localized to the endoplasmic reticulum.
The mutant protein, however, was found in membrane inclusions around the nucleus, and neural cells showed altered morphology indicating cell toxicity.
These findings suggest that mutant torsinA may lead to endoplasmic reticulum disruption and may possibly interfere with normal torsinA function. Our lab
recently discovered a novel torsinA interacting protein, which we have named printor for protein interactor of torsinA. To better characterize the interaction
between torsinA and printor, yeast two-hybrid interaction assays were performed to identify the binding regions necessary for the interaction. Given our
finding that printor interacts with itself in vivo, we made deletion constructs expressing various printor domains and analyzed the ability of the printor deletion
mutants to bind torsinA and printor in yeast two-hybrid interaction assays to identify the binding regions for printor self-interaction. In addition, we performed
yeast-two hybrid screens of a rat hippocampal cDNA library to find novel printor-binding partners. Further characterization of the interaction between torsinA
and printor, as well as identification of novel printor interacting proteins will yield insight into the role of printor in DYT1 pathogenesis.
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