Printor, a novel torsinA-interacting protein implicated in dystonia pathogenesis.

Early onset generalized dystonia (DYT1) is an autosomal dominant neurological disorder caused by deletion of a single glutamate residue (torsinA DeltaE) in the C-terminal region of the AAA(+) (ATPases associated with a variety of cellular activities) protein torsinA. The pathogenic mechanism by which torsinA DeltaE mutation leads to dystonia remains ...
unknown. Here we report the identification and characterization of a 628-amino acid novel protein, printor, that interacts with torsinA. Printor co-distributes with torsinA in multiple brain regions and co-localizes with torsinA in the endoplasmic reticulum. Interestingly, printor selectively binds to the ATP-free form but not to the ATP-bound form of torsinA, supporting a role for printor as a cofactor rather than a substrate of torsinA. The interaction of printor with torsinA is completely abolished by the dystonia-associated torsinA DeltaE mutation. Our findings suggest that printor is a new component of the DYT1 pathogenic pathway and provide a potential molecular target for therapeutic intervention in dystonia.
Mesh Terms:
Brain, Carrier Proteins, Cell Line, Cell Line, Tumor, Dystonia, Endoplasmic Reticulum, Gene Expression Regulation, Glycosylation, HeLa Cells, Humans, Models, Biological, Molecular Chaperones, Mutation, Protein Binding, Protein Structure, Tertiary, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Aug. 07, 2009
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