Dataset Information

A cytoplasmic dynein tail mutation impairs motor processivity.

ABSTRACT: 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) has 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 dynein from wild-type mice and the Legs at odd angles mutant mice. Using biochemical, single-molecule, and live-cell-imaging techniques, we find a marked inhibition of motor run-length in vitro and in vivo, and significantly altered motor domain coordination in the dynein from mutant mice. These results suggest a potential role for the dynein tail in motor function, and provide direct evidence for a link between single-motor processivity and disease.

SUBMITTER: Ori-McKenney KM

PROVIDER: S-EPMC3385513 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A cytoplasmic dynein tail mutation impairs motor processivity.

Ori-McKenney Kassandra M KM Xu Jing J Gross Steven P SP Vallee Richard B RB

Nature cell biology 20101121 12

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) has 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 dynein from wild-type mice and the Legs at odd angles mutant mice. Using biochemical, single-molecule, and live-cell-imaging tec ...[more]

PMID: 21102439

Similar Datasets

Project description:This study compares the role of electrostatics in the binding process between microtubules and two dynein microtubule-binding domains (MTBDs): cytoplasmic and axonemal. These two dyneins are distinctively different in terms of their functionalities: cytoplasmic dynein is processive, while axonemal dynein is involved in beating. In both cases, the binding requires frequent association/disassociation between the microtubule and MTBD, and involves highly negatively charged microtubules, including non-structured C-terminal domains (E-hooks), and an MTBD interface that is positively charged. This indicates that electrostatics play an important role in the association process. Here, we show that the cytoplasmic MTBD binds electrostatically tighter to microtubules than to the axonemal MTBD, but the axonemal MTBD experiences interactions with microtubule E-hooks at longer distances compared with the cytoplasmic MTBD. This allows the axonemal MTBD to be weakly bound to the microtubule, while at the same time acting onto the microtubule via the flexible E-hooks, even at MTBD⁻microtubule distances of 45 Å. In part, this is due to the charge distribution of MTBDs: in the cytoplasmic MTBD, the positive charges are concentrated at the binding interface with the microtubule, while in the axonemal MTBD, they are more distributed over the entire structure, allowing E-hooks to interact at longer distances. The dissimilarities of electrostatics in the cases of axonemal and cytoplasmic MTBDs were found not to result in a difference in conformational dynamics on MTBDs, while causing differences in the conformational states of E-hooks. The E-hooks' conformations in the presence of the axonemal MTBD were less restricted than in the presence of the cytoplasmic MTBD. In parallel with the differences, the common effect was found that the structural fluctuations of MTBDs decrease as either the number of contacts with E-hooks increases or the distance to the microtubule decreases.

Dataset Information

A cytoplasmic dynein tail mutation impairs motor processivity.

Publications

A cytoplasmic dynein tail mutation impairs motor processivity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets