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2018 ; 115
(3
): 537-542
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Cargo navigation across 3D microtubule intersections
#MMPMID29295928
Proc Natl Acad Sci U S A
2018[Jan]; 115
(3
): 537-542
PMID29295928
show ga
The eukaryotic cell's microtubule cytoskeleton is a complex 3D filament network.
Microtubules cross at a wide variety of separation distances and angles. Prior
studies in vivo and in vitro suggest that cargo transport is affected by
intersection geometry. However, geometric complexity is not yet widely
appreciated as a regulatory factor in its own right, and mechanisms that underlie
this mode of regulation are not well understood. We have used our recently
reported 3D microtubule manipulation system to build filament crossings de novo
in a purified in vitro environment and used them to assay kinesin-1-driven model
cargo navigation. We found that 3D microtubule network geometry indeed
significantly influences cargo routing, and in particular that it is possible to
bias a cargo to pass or switch just by changing either filament spacing or angle.
Furthermore, we captured our experimental results in a model which accounts for
full 3D geometry, stochastic motion of the cargo and associated motors, as well
as motor force production and force-dependent behavior. We used a combination of
experimental and theoretical analysis to establish the detailed mechanisms
underlying cargo navigation at microtubule crossings.