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

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Kazuka G OhashiWilliam O Hancock

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 ...Continue Reading

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Citations

Jun 24, 2020·Proceedings of the National Academy of Sciences of the United States of America·Brandon M BenselE Michael Ostap
Jun 17, 2020·Journal of Cell Science·Marcus BraunZdenek Lansky
Sep 18, 2020·Bulletin of Mathematical Biology·Maria-Veronica CiocanelScott A McKinley
Jan 18, 2020·Biophysical Journal·Jonathon Howard, William O Hancock
Mar 11, 2021·Molecular Biology of the Cell·Oane J GrosFlorian Berger
Jun 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Paulomi SanghaviRoop Mallik

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