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A Cytoplasmic Dynein Tail Mutation Impairs Motor Processivity

Mutations in the tail of the cytoplasmic dynein molecule have been reported to cause neurodegenerative disease in mice. The mutant mouse strain Legs at Odd Angles (Loa) exhibits impaired retrograde axonal transport, but the molecular deficiencies in the mutant dynein molecule, and how they contribut...

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Detalles Bibliográficos
Autores principales: Ori-McKenney, Kassandra M., Xu, Jing, Gross, Steven P., Vallee, Richard B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385513/
https://www.ncbi.nlm.nih.gov/pubmed/21102439
http://dx.doi.org/10.1038/ncb2127
Descripción
Sumario:Mutations in the tail of the cytoplasmic dynein molecule have been reported to cause neurodegenerative disease in mice. The mutant mouse strain Legs at Odd Angles (Loa) exhibits impaired retrograde axonal transport, but the molecular deficiencies in the mutant dynein molecule, and how they contribute to neurodegeneration, are unknown. To address these questions, we purified wild-type and mutant mouse dynein. Using biochemical, single molecule, and live cell imaging techniques, we find a strong inhibition of motor run-length in vitro and in vivo, and significantly altered motor domain coordination in the mutant dynein. These results suggest a potential role for the dynein tail in motor function, and provide the first direct evidence for a link between single-motor processivity and disease.