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Cited by 521Microtubule and mitosis dynamicsstochastic dynamics and bifurcationCellular Mechanics and Interactions

Tug-of-war as a cooperative mechanism for bidirectional cargo transport by molecular motors

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Müller, Melanie J. I., Klumpp, Stefan, Lipowsky, Reinhard·2008·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0706825105PMC PMC2290779
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Abstract

Intracellular transport is based on molecular motors that pull cargos along cytoskeletal filaments. One motor species always moves in one direction, e.g., conventional kinesin moves to the microtubule plus end, whereas cytoplasmic dynein moves to the microtubule minus end. However, many cellular cargoes are observed to move bidirectionally, involving both plus- and minus-end-directed motors. The presumably simplest mechanism for such bidirectional transport is provided by a tug-of-war between the two motor species. This mechanism is studied theoretically using the load-dependent transport properties of individual motors as measured in single-molecule experiments. In contrast to previous expectations, such a tug-of-war is found to be highly cooperative and to exhibit seven different motility regimes depending on the precise values of the single motor parameters. The sensitivity of the transport process to small parameter changes can be used by the cell to regulate its cargo traffic.

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  • Our results are consistent with a tug-of-war mechanism, in which tau acts as a selective barrier that preferentially inhibits kinesins-1 and -3, thereby shifting the balance toward dynein-driven transport.

    “Our results are consistent with a tug-of-war mechanism, in which tau acts as a selective barrier that preferentially inhibits kinesins-1 and -3, thereby shifting the balance toward dynein-driven transport”

    From Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons (2026) · cites this paper as Müller et al., 2008

    The Discussion (p. 6) supports tug-of-war as a mechanism for bidirectional transport, and the Results (p. 5) show that changes in motor properties can shift the direction of transport. Our copy does not identify tau as a selective barrier or report preferential inhibition of kinesins-1 and -3, so it does not support that specific explanation for a shift toward dynein-driven transport. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In one model, direction of travel is the outcome of a tug of war between the opposing motors associated with the cargo, and a change in direction is effected by a change in the relative number of engaged kinesin-1 and dynein molecules.

    “In one model, direction of travel is the outcome of a tug of war between the opposing motors associated with the cargo. A change in direction is effected by a change in the relative number of engaged kinesin-1 and dynein molecules (Welte, 2004; Müller et al., 2008).”

    From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Müller et al., 2008

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Related

Authors
Müller, M. J. I., Klumpp, S., & Lipowsky, R.
Affiliations
  • Max Planck Institute of Colloids and Interfaces (DE)
  • Max Planck Society (DE)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2008-03-25
Volume
105
Issue
12
Pages
4609-4614
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0706825105
PMC
PMC2290779
OpenAlex
W2078056153
Cited by
521
References
39
Citations by year
2026: 14 · 2025: 18 · 2024: 11 · 2023: 19 · 2022: 22 · 2021: 24 · 2020: 28 · 2019: 30 · 2018: 33 · 2017: 31 · 2016: 34 · 2015: 25 · 2014: 29 · 2013: 33 · 2012: 41
FWCI
18.83
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • arXiv (Cornell University) (submittedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Max Planck Digital Library (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • arXiv (Cornell University)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › stochastic dynamics and bifurcation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
tug-of-war, molecular motors, kinesin, cytoplasmic dynein, intracellular transport, microtubules
MeSH terms
Animals, Biological Transport, Cell Movement, Drosophila, Dyneins, Microtubules, Models, Biological, Mutation, Kinesins, Cell Polarity, Molecular Motor Proteins, Lipid Metabolism

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