Huntingtin Facilitates Dynein/Dynactin-mediated Vesicle Transport.
From: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Jun 2007
- ISSN: 0027-8424
- Volume: 104
- Issue: 24
- Pages: 10045-50
- Medium: Print
- Language: English
- Citation (JAMA): Caviston Juliane P, Ross Jennifer L, Antony Sheila M, et al. Huntingtin Facilitates Dynein/Dynactin-mediated Vesicle Transport.. Proc. Natl. Acad. Sci. U.S.A. Jun 2007;104:10045-50
Abstract
Cytoplasmic dynein is a multisubunit microtubule motor complex that, together with its activator, dynactin, drives vesicular cargo toward the minus ends of microtubules. Huntingtin (Htt) is a vesicle-associated protein found in both neuronal and nonneuronal cells that is thought to be involved in vesicular transport. In this study, we demonstrate through yeast two-hybrid and affinity chromatography assays that Htt and dynein intermediate chain interact directly; endogenous Htt and dynein co-immunoprecipitate from mouse brain cytosol. Htt RNAi in HeLa cells results in Golgi disruption, similar to the effects of compromising dynein/dynactin function. In vitro studies reveal that Htt and dynein are both present on vesicles purified from mouse brain. Antibodies to Htt inhibited vesicular transport along microtubules, suggesting that Htt facilitates dynein-mediated vesicle motility. In vivo inhibition of dynein function results in a significant redistribution of Htt to the cell periphery, suggesting that dynein transports Htt-associated vesicles toward the cell center. Together these findings indicate that Htt binds to dynein and acts in a complex along with dynactin and Htt-associated protein-1 to facilitate vesicular transport.
Mesh Headings (Keywords): Animals, Biological Transport, Brain Chemistry, Cattle, Chromatography, Affinity, Cytoplasmic Vesicles, Cytosol, Dynein ATPase, Golgi Apparatus, Hela Cells, Humans, Immunohistochemistry, Mice, Mice, Transgenic, Microtubules, Nerve Tissue Proteins, Nuclear Proteins, Precipitin Tests, RNA Interference, Sensitivity and Specificity, Two-Hybrid System Techniques
Check for Full Text / PubMed Unique Identifier (PMID): 17548833
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