Background: Early-onset torsion dystonia is a hyperkinetic movement disorder caused by a deletion of 1 glutamic acid residue in torsin A protein, a novel 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 torsin 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 analyzed by Western blot analysis and immunohistochemistry in human postmortem brain tissues.
Results: We generated polyclonal antipeptide antibodies directed against human torsin A and torsin B proteins. In Western blot analysis of normal human brain homogenates, the antibodies specifically recognized 38-kd endogenous torsin A and 62-kd endogenous torsin B. Absorption controls showed that labeling was blocked by cognate peptide used for immunization. Immunolocalization studies revealed that torsin A and torsin B were widely expressed throughout the human central nervous system. Both proteins displayed cytoplasmic distribution, although torsin B localization in some neurons was perinuclear. 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 torsin proteins in synaptic functioning.