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Cited by 56Microtubule and mitosis dynamicsCellular Mechanics and Interactionsstochastic dynamics and bifurcation

Motor dynamics underlying cargo transport by pairs of kinesin-1 and kinesin-3 motors

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Arpağ, Göker, Norris, Stephen R., Mousavi, S. Iman, Soppina, Virupakshi, Verhey, Kristen J., Hancock, William O., Tüzel, Erkan·2019·Biophysical Journal
DOI 10.1016/j.bpj.2019.01.036PMC PMC6428962
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Abstract

Intracellular cargo transport by kinesin family motor proteins is crucial for many cellular processes, particularly vesicle transport in axons and dendrites. In a number of cases, the transport of specific cargo is carried out by two classes of kinesins that move at different speeds and thus compete during transport. Despite advances in single-molecule characterization and modeling approaches, many questions remain regarding the effect of intermotor tension on motor attachment/reattachment rates during cooperative multimotor transport. To understand the motor dynamics underlying multimotor transport, we analyzed the complexes of kinesin-1 and kinesin-3 motors attached through protein scaffolds moving on immobilized microtubules in vitro. To interpret the observed behavior, simulations were carried out using a model that incorporated motor stepping, attachment/detachment rates, and intermotor force generation. In single-molecule experiments, isolated kinesin-3 motors moved twofold faster and had threefold higher landing rates than kinesin-1. When the positively charged loop 12 of kinesin-3 was swapped with that of kinesin-1, the landing rates reversed, indicating that this "K-loop" is a key determinant of the motor reattachment rate. In contrast, swapping loop 12 had negligible effects on motor velocities. Two-motor complexes containing one kinesin-1 and one kinesin-3 moved at different speeds depending on the identity of their loop 12, indicating the importance of the motor reattachment rate on the cotransport speed. Simulations of these loop-swapped motors using experimentally derived motor parameters were able to reproduce the experimental results and identify best fit parameters for the motor reattachment rates for this geometry. Simulation results also supported previous work, suggesting that kinesin-3 microtubule detachment is very sensitive to load. Overall, the simulations demonstrate that the transport behavior of cargo carried by pairs of kinesin-1 and -3 motors are determined by three properties that differ between these two families: the unloaded velocity, the load dependence of detachment, and the motor reattachment rate.

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Authors
Arpağ, G., Norris, S. R., Mousavi, S. I., Soppina, V., Verhey, K. J., Hancock, W. O., & Tüzel, E.
Affiliations
  • Worcester Polytechnic Institute (US)
  • University of Michigan (US)
  • Pennsylvania State University (US)
Corresponding author
  • Hancock, William O.
  • Tüzel, Erkan
ORCID
Venue
Biophysical Journal
Publisher
Elsevier BV
Published
2019-03
Volume
116
Issue
6
Pages
1115-1126
ISSN
0006-3495 (ISSN-L)
DOI
10.1016/j.bpj.2019.01.036
PMC
PMC6428962
OpenAlex
W2914041924
Cited by
56
References
3
Citations by year
2026: 9 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 8 · 2020: 15 · 2019: 3
FWCI
4.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Biophysical Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (R01GM100076, R01GM121679, R01GM070862)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › stochastic dynamics and bifurcation
Keywords
kinesin-1, kinesin-3, freight transport, motor speed, microtubule detachment, load dependence, axonal transport, vesicle trafficking, motor dynamics
MeSH terms
Animals, Biological Transport, Chlorocebus aethiops, Models, Biological, Kinesins, COS Cells

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