Source:http://linkedlifedata.com/resource/pubmed/id/18384641
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2008-7-9
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| pubmed:abstractText |
Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease caused by a small expansion of CAG repeats in the sequence coding for the cytoplasmic C-terminal region of the Ca(v)2.1 subunit of P/Q-type calcium channels. We have tested the toxicity of mutated Ca(v)2.1 C-terminal domains expressed in the plasma membrane. In COS-7 cells, CD4-green fluorescent protein fused to Ca(v)2.1 C-terminal domains containing expanded 24 polyglutamine (Q) tracts displayed increased toxicity and stronger expression at the cell surface relative to 'normal' 12 Q tracts, partially because of reduced endocytosis. Glutathione S-transferase pull-down and proteomic analysis indicated that Ca(v)2.1 C-termini interact with the heavy and light chains of cerebellar myosin IIB, a molecular motor protein. This interaction was confirmed by coimmunoprecipitation from rat cerebellum and COS-7 cells and shown to be direct by binding of in vitro-translated (35)S-myosin IIB heavy chain. In COS-7 cells, incremented polyglutamine tract length increased the interaction with myosin IIB. Furthermore, the myosin II inhibitor blebbistatin reversed the effects of polyglutamine expansion on plasma membrane expression. Our findings suggest a key role of myosin IIB in promoting accumulation of mutant Ca(v)2.1Ct at the plasma membrane and suggest that this gain of function might contribute to the pathogenesis of SCA6.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Nonmuscle Myosin Type IIB,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/polyglutamine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
1600-0854
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
9
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1088-100
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| pubmed:meshHeading |
pubmed-meshheading:18384641-Amino Acid Sequence,
pubmed-meshheading:18384641-Animals,
pubmed-meshheading:18384641-Antigens, CD4,
pubmed-meshheading:18384641-COS Cells,
pubmed-meshheading:18384641-Calcium Channels,
pubmed-meshheading:18384641-Cercopithecus aethiops,
pubmed-meshheading:18384641-Endocytosis,
pubmed-meshheading:18384641-Glutathione Transferase,
pubmed-meshheading:18384641-Humans,
pubmed-meshheading:18384641-Mice,
pubmed-meshheading:18384641-Molecular Sequence Data,
pubmed-meshheading:18384641-Neurodegenerative Diseases,
pubmed-meshheading:18384641-Nonmuscle Myosin Type IIB,
pubmed-meshheading:18384641-Peptides,
pubmed-meshheading:18384641-Protein Structure, Tertiary,
pubmed-meshheading:18384641-Rats,
pubmed-meshheading:18384641-Sequence Homology, Amino Acid,
pubmed-meshheading:18384641-Spinocerebellar Ataxias
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| pubmed:year |
2008
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| pubmed:articleTitle |
Toxicity and endocytosis of spinocerebellar ataxia type 6 polyglutamine domains: role of myosin IIb.
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| pubmed:affiliation |
INSERM U641, Marseille F-13916, France. marqueze@ciml.univ-mrs.fr
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|