Multiple kinesins induce tension for smooth cargo transport
Abstract
How cargoes move within a crowded cell—over long distances and at speeds nearly the same as when moving on unimpeded pathway—has long been mysterious. Through an in vitro force-gliding assay, which involves measuring nanometer displacement and piconewtons of force, we show that multiple mammalian kinesin-1 (from 2-8) communicate in a team by inducing tension (up to 4 pN) on the cargo. Kinesins adopt two distinct states, with one-third slowing down the microtubule and two-thirds speeding it up. Resisting kinesins tend to come off more rapidly than, and speed up when pulled by driving kinesins, implying an asymmetric tug-of-war. Furthermore, kinesins dynamically interact to overcome roadblocks, occasionally combining their forces. Consequently, multiple kinesins acting as a team may play a significant role in facilitating smooth cargo motion in a dense environment. This is one of few cases in which single molecule behavior can be connected to ensemble behavior of multiple motors.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
National Institutes of Health (GM108578)
- Paul R Selvin
National Science Foundation (1430124)
- Paul R Selvin
National Institutes of Health (GM078097)
- Kathleen M Trybus
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Tjioe et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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