Load‐dependent detachment kinetics plays a key role in bidirectional cargo transport by kinesin and dynein

Kazuka G. Ohashi; Lifeng Han; Brandon Mentley; Jiaxuan Wang; John Fricks; William O. Hancock

doi:10.1111/tra.12639

journal article Mar 15, 2019

Load‐dependent detachment kinetics plays a key role in bidirectional cargo transport by kinesin and dynein

Kazuka G. Ohashi Lifeng Han Brandon Mentley Jiaxuan Wang

John Fricks William O. Hancock

Traffic Vol. 20 No. 4 pp. 284-294 · Wiley

View at Publisher Save 10.1111/tra.12639

Abstract

Bidirectional cargo transport along microtubules is carried out by opposing teams of kinesin and dynein motors. Despite considerable study, the factors that determine whether these competing teams achieve net anterograde or retrograde transport in cells remain unclear. The goal of this work is to use stochastic simulations of bidirectional transport to determine the motor properties that most strongly determine overall cargo velocity and directionality. Simulations were carried out based on published optical tweezer characterization of kinesin‐1 and kinesin‐2, and for available data for cytoplasmic dynein and the dynein‐dynactin‐BicD2 (DDB) complex. By varying dynein parameters and analyzing cargo trajectories, we find that net cargo transport is predicted to depend minimally on the dynein stall force, but strongly on dynein load‐dependent detachment kinetics. In simulations, dynein is dominated by kinesin‐1, but DDB and kinesin‐1 are evenly matched, recapitulating recent experimental work. Kinesin‐2 competes less well against dynein and DDB, and overall, load‐dependent motor detachment is the property that most determines a motor's ability to compete in bidirectional transport. It follows that the most effective intracellular regulators of bidirectional transport are predicted to be those that alter motor detachment kinetics rather than motor velocity or stall force.

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References

Details

Published: Mar 15, 2019
Vol/Issue: 20(4)
Pages: 284-294
License: View

Authors

K

Kazuka G. Ohashi

Department of Biomedical Engineering Penn State University University Park Pennsylvania

L

Lifeng Han

School of Mathematical and Statistical Sciences Arizona State University Tempe Arizona

B

Brandon Mentley

Department of Biomedical Engineering Penn State University University Park Pennsylvania

J

Jiaxuan Wang

Department of Biomedical Engineering Penn State University University Park Pennsylvania

J

John Fricks

School of Mathematical and Statistical Sciences Arizona State University Tempe Arizona

W

William O. Hancock

Department of Biomedical Engineering Penn State University University Park Pennsylvania

Funding

National Institutes of Health Award: R01GM122082

Cite This Article

Kazuka G. Ohashi, Lifeng Han, Brandon Mentley, et al. (2019). Load‐dependent detachment kinetics plays a key role in bidirectional cargo transport by kinesin and dynein. Traffic, 20(4), 284-294. https://doi.org/10.1111/tra.12639

Load‐dependent detachment kinetics plays a key role in bidirectional cargo transport by kinesin and dynein

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