Cellular Distribution of Torsin A and Torsin B in Normal Human Brain

Konakova, Marina; Huynh, Duong P.; Yong, William H.; Pulst, Stefan M.

doi:10.1001/archneur.58.6.921

Cited by 79 publications

(52 citation statements)

References 24 publications

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“…This relationship is consistent with the normal role of this protein in cytoskeletal dynamics 1 and its immunostaining in axons. 3,4 However, the regional specificity of the DTI results is inconsistent with postmortem findings in which the distribution of torsin A immunostaining in DYT1 carriers was found to be essentially normal. 18,19 In summary, our data suggest that altered microstructural integrity of precentral motor pathways may constitute a vulnerability factor for the development of dystonia in DYT1 carriers.…”

Section: Discussionmentioning

confidence: 58%

Microstructural white matter changes in carriers of the DYT1 gene mutation

Carbon

Kingsley

et al. 2004

Annals of Neurology

129

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We tested the hypothesis that the DYT1 genotype is associated with a disorder of anatomical connectivity involving primarily the sensorimotor cortex. We used diffusion tensor magnetic resonance imaging (DTI) to assess the microstructure of white matter pathways in mutation carriers and control subjects. Fractional anisotropy (FA), a measure of axonal integrity and coherence, was reduced (p < 0.005) in the subgyral white matter of the sensorimotor cortex of DYT1 carriers. Abnormal anatomical connectivity of the supplementary motor area may contribute to the susceptibility of DYT1 carriers to develop clinical manifestations of dystonia.

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Section: Discussionmentioning

confidence: 58%

Microstructural white matter changes in carriers of the DYT1 gene mutation

Carbon

Kingsley

et al. 2004

Annals of Neurology

129

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“…In these and other studies, it is apparent that torsinA undergoes anterograde transport along neuronal processes to terminals, presumably in association with the ER and/or vesicles (12,(57)(58)(59), apparently mediated by kinesin. Ultrastructural studies in primate brain demonstrated torsinA immunoreactivity associated with small clear vesicles in symmetric synapses in the striatum (59).…”

Section: Nx(t/s) Asnmentioning

confidence: 54%

The Early Onset Dystonia Protein TorsinA Interacts with Kinesin Light Chain 1

Kamm

Boston

Hewett

et al. 2004

Journal of Biological Chemistry

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Early onset dystonia is a movement disorder caused by loss of a glutamic acid residue (Glu 302/303 ) in the carboxyl-terminal portion of the AAA ؉ protein, torsinA. We identified the light chain subunit (KLC1) of kinesin-I as an interacting partner for torsinA, with binding occurring between the tetratricopeptide repeat domain of KLC1 and the carboxyl-terminal region of torsinA. Coimmunoprecipitation analysis demonstrated that wildtype torsinA and kinesin-I form a complex in vivo. In cultured cortical neurons, both proteins co-localized along processes with enrichment at growth cones. Wildtype torsinA expressed in CAD cells co-localized with endogenous KLC1 at the distal end of processes, whereas mutant torsinA remained confined to the cell body. Subcellular fractionation of adult rat brain revealed torsinA and KLC associated with cofractionating membranes, and both proteins were co-immunoprecipitated after cross-linking cytoplasmically oriented proteins on isolated rat brain membranes. These studies suggest that wild-type torsinA undergoes anterograde transport along microtubules mediated by kinesin and may act as a molecular chaperone regulating kinesin activity and/or cargo binding.

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“…TorsinA is widely distributed throughout the central nervous system, and has been detected specifically in the cerebral cortex, striatum, substantia nigra pars compacta, thalamus, hippocampus, cerebellum, midbrain, pons and spinal cord (Augood et al, 1998(Augood et al, , 1999Shashidharan et al, 2000;Konakova et al, 2001;Rostasy et al, 2003). Within neurons, wild-type torsinA localizes to the endoplasmic reticulum (Liu et al, 2003;Naismith et al, 2004;Hewett et al, 2007), while mutant torsinA protein is found in the perinuclear space (Hewett et al, 2000;Gonzalez-Alegre and Paulson, 2004;Goodchild and Dauer, 2004).…”

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confidence: 99%

Commentary: Dopaminergic dysfunction in DYT1 dystonia

Wichmann

2008

Experimental Neurology

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A three-base-pair deletion in the torsinA gene leads to generalized torsion dystonia (DYT1) in humans, an often devastating movement disorder in which voluntary movements are disrupted by sustained muscle spasms and abnormal limb posturing. In a recent issue of Experimental Neurology, Zhao et al. (2008) have provided a thorough behavioral, anatomic, and biochemical characterization of a mouse line that over-expresses human mutant torsinA, with particular emphasis on the possible role of dopaminergic dysfunction in these animals. This commentary provides an overview of the clinical and genetic features of the human disease and of the available transgenic mouse models for DYT1 dystonia, and discusses the evidence favoring the role of dopamine in the clinical manifestations of the disease.

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Cellular Distribution of Torsin A and Torsin B in Normal Human Brain

Abstract: 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.

Cited by 79 publications

References 24 publications

Microstructural white matter changes in carriers of the DYT1 gene mutation

Microstructural white matter changes in carriers of the DYT1 gene mutation

The Early Onset Dystonia Protein TorsinA Interacts with Kinesin Light Chain 1

Commentary: Dopaminergic dysfunction in DYT1 dystonia

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