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Cellular Distribution of Torsin A and Torsin B in Normal Human Brain
Marina Konakova, PhD;
Duong P. Huynh, PhD;
William Yong, MD;
Stefan M. Pulst, MD
Arch Neurol. 2001;58:921-927.
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.
From the Rose Moss Laboratory for Parkinson's and Neurodegenerative
Diseases, Burns and Allen Research Institute (Drs Konakova, Huynh, and Pulst),
the Department of Surgical Pathology (Dr Yong), and the Division of Neurology
(Dr Pulst), Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles,
Calif.
Corresponding author and reprints: Stefan M. Pulst, MD, Division
of Neurology, Cedars-Sinai Medical Center, UCLA School of Medicine, 8700 Beverly
Blvd, Los Angeles, CA 90048 (e-mail: stefan.pulst{at}cshs.org).
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