Printor, a Novel TorsinA-interacting Protein Implicated in Dystonia Pathogenesis*
AUTOR(ES)
Giles, Lisa M.
FONTE
American Society for Biochemistry and Molecular Biology
RESUMO
Early onset generalized dystonia (DYT1) is an autosomal dominant neurological disorder caused by deletion of a single glutamate residue (torsinA ΔE) in the C-terminal region of the AAA+ (ATPases associated with a variety of cellular activities) protein torsinA. The pathogenic mechanism by which torsinA ΔE 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 ΔE 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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2755898Documentos Relacionados
- TorsinA and torsion dystonia: Unraveling the architecture of the nuclear envelope
- Effect of torsinA on membrane proteins reveals a loss of function and a dominant-negative phenotype of the dystonia-associated ΔE-torsinA mutant
- Mislocalization to the nuclear envelope: An effect of the dystonia-causing torsinA mutation
- Characterization of a Novel Yeast SNARE Protein Implicated in Golgi Retrograde Traffic
- Identification of a novel Rac1-interacting protein involved in membrane ruffling.