Huntingtin facilitates dynein/dynactin-mediated vesicle transport

Juliane P. Caviston, Jennifer L. Ross, Sheila M. Antony, Mariko Tokito, Erika L.F. Holzbaur

Research output: Contribution to journalArticle

178 Scopus citations

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 coimmunoprecipitate 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.

Original languageEnglish (US)
Pages (from-to)10045-10050
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number24
DOIs
StatePublished - Jun 12 2007

Keywords

  • Bidirectional motility
  • Huntington's disease
  • Membrane trafficking
  • Microtubule motility
  • Molecular motors

ASJC Scopus subject areas

  • General

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