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Motor Coordination via a Tug-of-War Mechanism Drives Bidirectional Vesicle Transport
Open accessAbstract
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.
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“Support for this model includes studies of neuronal vesicles (Hendricks et al., 2010) and endosomes (Soppina et al., 2009).”
From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Hendricks et al., 2010
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Metadata
- Authors
- Hendricks, A. G., Perlson, E., Ross, J. L., Schroeder, H. W., Tokito, M., & Holzbaur, E. L. F.
- Affiliations
- University of Pennsylvania (US)
- University of Massachusetts Amherst (US)
- Corresponding author
- Holzbaur, Erika L.F.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 20
- Issue
- 8
- Pages
- 697-702
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC2908734
- OpenAlex
- W1972398314
- Cited by
- 423
- References
- 29
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 16 · 2023: 19 · 2022: 13 · 2021: 24 · 2020: 26 · 2019: 28 · 2018: 36 · 2017: 31 · 2016: 30 · 2015: 20 · 2014: 36 · 2013: 27 · 2012: 38
- FWCI
- 15.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- National Institutes of Health (1f32gm075754-01)
- National Institute of General Medical Sciences (GM-48661, P01GM087253, GM087253, F32 GM075754, R01GM048661, GM071339, 1F32GM075754, T32GM071339)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › stochastic dynamics and bifurcation
- Keywords
- kinesin, dynein, motor coordination, tug-of-war model, directional switching, processive motility, in vitro reconstitution, particle tracking
- MeSH terms
- Dynactin Complex, Animals, Biological Transport, Dyneins, Mice, Transgenic, Microtubule-Associated Proteins, Microtubules, Neurons, Recombinant Fusion Proteins, Stress, Mechanical, Kinesins, Transport Vesicles, Mice
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