title: TorsinA and dystonia: from nuclear envelope to synapse.
abstract: A GAG deletion in the DYT1 gene is responsible for the autosomal dominant movement disorder, early onset primary torsion dystonia, which is characterised by involuntary sustained muscle contractions and abnormal posturing of the limbs. The mutation leads to deletion of a single glutamate residue in the C-terminus of the protein torsinA, a member of the AAA+ ATPase family of proteins with multiple functions. Since no evidence of neurodegeneration has been found in DYT1 patients, the dystonic phenotype is likely to be the result of neuronal functional defect(s), the nature of which is only partially understood. Biochemical, structural and cell biological studies have been performed in order to characterise torsinA. These studies, together with the generation of several animal models, have contributed to identify cellular compartments and pathways, including the cytoskeleton and the nuclear envelope, the secretory pathway and the synaptic vesicle machinery where torsinA function may be crucial. However, the role of torsinA and the correlation between the dysfunction caused by the mutation and the dystonic phenotype remain unclear. This review provides an overview of the findings of the last ten years of research on torsinA, a critical evaluation of the different models proposed and insights towards future avenues of research.
authors.affiliation: Department of Clinical Neurosciences, UCL Institute of Neurology, London, UK. a.granata@medsch.ucl.ac.uk
authors.forename: Alessandra
authors.initials: A
authors.lastname: Granata
authors.forename: Giampietro
authors.initials: G
authors.lastname: Schiavo
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Warner
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D004195:Disease Models, Animal; D004421:Dystonia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000473:pathology
chemical_list: D018832:Molecular Chaperones; C108175:TOR1A protein, human