What is it about?
Tiny Kinesin-1 molecular motors transport vesicles containing essential cellular resources along the cell's dense and complex 3-dimensional microtubule highway. Despite the importance of this most basic process, how kinesin-1s maneuver their intracellular cargoes through the numerous microtubule intersections towards their destination is still a mystery. Therefore, we developed a model that mimics this important intracellular transport system on a microscope glass slide, challenging kinesin-1s to transport vesicle-like liposomes through 3-dimensional microtubule intersections as these molecular motors would encounter inside cells on their way to their destination for delivery.
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Photo by National Cancer Institute on Unsplash
Why is it important?
Intracellular cargoes that are transported and delivered by kinesin-1 molecular motors, such as insulin granules, are critical for normal cellular and human health.
Perspectives
Surprisingly, when challenged with a 3-dimensional microtubule intersection, kinesin-1 molecular motors are biased to maneuver their tiny vesicle cargoes straight through the intersection rather than turning even when the microtubule intersection acts as a physical barrier; a result like that of an unrelated molecular motor cargo transporter, myosin Va . Using computer simulations, we propose that these molecular motors share a fundamental mechanism for navigating cargoes through cytoskeletal highway intersections en route to their intracellular destination.
David Warshaw
University of Vermont
By reconstituting a more realistic cargo (the liposome with a team of kinesins) at the lab bench and challenging that cargo with a realistic obstacle (a 3D intersection) created on a microscope slide, we made the surprising observation that kinesin-1 deals with intersections in the same manner as the unrelated actin-based transport motor myosin V. By combining in vitro reconstitutions with computer based mathematical simulations, we were able to understand more clearly how this result comes to pass, and even can visualize this by rendering the simulations into movies. This shows how powerful and fun interdisciplinary science can be.
Brandon Bensel
University of Vermont
Read the Original
This page is a summary of: Kinesin-1-transported liposomes prefer to go straight in 3D microtubule intersections by a mechanism shared by other molecular motors, Proceedings of the National Academy of Sciences, July 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2407330121.
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