Cellular distribution of torsin A and torsin B in normal human brain

Background: Early-onset torsion dystonia is a hyperkinetic movement disorde r caused by a deletion of 1 glutamic acid residue in torsin A protein, a no vel member of the AAA family of adenosine triphosphatases. No mutation has been found so far in the closely related torsin B protein. Little is known about the molecular basis of the disease, and the cellular functions of tor sin proteins remain to be investigated. Objective: To study the regional, cellular, and subcellular distribution of the torsin A and torsin B proteins. Methods: Expression of torsin proteins in the central nervous system was an alyzed by Western blot analysis and immunohistochemistry in human postmorte m brain tissues. Results: We generated polyclonal antipeptide antibodies directed against hu man torsin A and torsin B proteins. In Western blot analysis of normal huma n brain homogenates, the antibodies specifically recognized 38-kd endogenou s torsin A and 62-kd endogenous torsin B. Absorption controls showed that l abeling was blocked by cognate peptide used for immunization. Immunolocaliz ation studies revealed that torsin A and torsin B were widely expressed thr oughout the human central nervous system. Both proteins displayed cytoplasm ic distribution, although torsin B localization in some neurons was perinuc lear. Strong labeling of neuronal processes was detected for both proteins. Conclusions: Torsin A and torsin B have similar distribution in the central nervous system, although their subcellular localization is not identical. Strong expression in neuronal processes points to a potential role for tors in proteins in synaptic functioning.