Source:http://linkedlifedata.com/resource/pubmed/id/10814722
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
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| pubmed:dateCreated |
2000-8-29
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| pubmed:abstractText |
Early-onset torsion dystonia is a hereditary movement disorder thought to be caused by decreased release of dopamine into the basal ganglia, without apparent neuronal degeneration. Recent cloning of the gene responsible for this disease, TOR1A (DYT1), identified the encoded protein, torsinA, as a member of the AAA+ superfamily of chaperone proteins and revealed highest levels of expression in dopaminergic neurons in human brain. Most cases of this disease are caused by a deletion of one glutamic acid residue in the C-terminal region of the protein. Antibodies generated against torsinA revealed expression of a predominant immunoreactive protein species similar to the predicted size of 37.8 kDa in neural, glial and fibroblastic lines by western blot analysis. This protein is N-glycosylated with high mannose content and not, apparently, phosphoryl-ated. Overexpression of torsinA in mouse neural CAD cells followed by immunocytochemistry, revealed a dramatically different pattern of distribution for wild-type and mutant forms of the protein. The wild-type protein was found throughout the cytoplasm and neurites with a high degree of co-localization with the endoplasmic reticulum (ER) marker, protein disulfide isomerase. In contrast, the mutant protein accumulated in multiple, large inclusions in the cytoplasm around the nucleus. These inclusions were composed of membrane whorls, apparently derived from the ER. If disrupted processing of the mutant protein leads to its accumulation in multilayer membranous structures in vivo, these may interfere with membrane trafficking in neurons.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dyt1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Molecular Chaperones,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Disulfide-Isomerases,
http://linkedlifedata.com/resource/pubmed/chemical/TOR1A protein, human
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
0964-6906
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
22
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| pubmed:volume |
9
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1403-13
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:10814722-Animals,
pubmed-meshheading:10814722-Blotting, Western,
pubmed-meshheading:10814722-Carrier Proteins,
pubmed-meshheading:10814722-Cell Membrane,
pubmed-meshheading:10814722-Cells, Cultured,
pubmed-meshheading:10814722-Dystonia Musculorum Deformans,
pubmed-meshheading:10814722-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:10814722-Endoplasmic Reticulum,
pubmed-meshheading:10814722-Glycosylation,
pubmed-meshheading:10814722-Golgi Apparatus,
pubmed-meshheading:10814722-Humans,
pubmed-meshheading:10814722-Immunohistochemistry,
pubmed-meshheading:10814722-Mice,
pubmed-meshheading:10814722-Molecular Chaperones,
pubmed-meshheading:10814722-Mutation,
pubmed-meshheading:10814722-Neurons,
pubmed-meshheading:10814722-Precipitin Tests,
pubmed-meshheading:10814722-Protein Disulfide-Isomerases
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| pubmed:year |
2000
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| pubmed:articleTitle |
Mutant torsinA, responsible for early-onset torsion dystonia, forms membrane inclusions in cultured neural cells.
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| pubmed:affiliation |
Molecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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