Motor Coordination via a Tug-of-War Mechanism Drives Bidirectional Vesicle Transport

Adam G. Hendricks, Eran Perlson, Jennifer L. Ross, Harry W. Schroeder, Mariko Tokito, Erika L.F. Holzbaur

Research output: Contribution to journalArticlepeer-review

264 Scopus citations

Abstract

The microtubule motors kinesin and dynein function collectively to drive vesicular transport. High-resolution tracking of vesicle motility in the cell indicates that transport is often bidirectional, characterized by frequent directional changes. However, the mechanisms coordinating the collective activities of oppositely oriented motors bound to the same cargo are not well understood. To examine motor coordination, we purified neuronal transport vesicles and analyzed their motility via automated particle tracking with nanometer resolution. The motility of purified vesicles reconstituted in vitro closely models the movement of LysoTracker-positive vesicles in primary neurons, where processive bidirectional motility is interrupted with frequent directional switches, diffusional movement, and pauses. Quantitative analysis indicates that vesicles copurify with a low number of stably bound motors: one to five dynein and one to four kinesin motors. These observations compare well to predictions from a stochastic tug-of-war model, where transport is driven by the force-dependent kinetics of teams of opposing motors in the absence of external regulation. Together, these observations indicate that vesicles move robustly with a small complement of tightly bound motors and suggest an efficient regulatory scheme for bidirectional motility where small changes in the number of engaged motors manifest in large changes in the motility of cargo.

Original languageEnglish (US)
Pages (from-to)697-702
Number of pages6
JournalCurrent Biology
Volume20
Issue number8
DOIs
StatePublished - Apr 27 2010
Externally publishedYes

Keywords

  • CELLBIO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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