Mechanism of Bi-directional In-vivo Transport by Multiple Molecular Motors

 Bi-directional motion of sub-cellular cargos such as mRNA particles, virus particles,
endosomes, and lipid droplets is quite common. Because molecular motors are
predominantly uni-directional, these back-and-forth motions along microtubules clearly
involve contributions from both plus-end kinesin motors, and minus-end dynein motors.
While the instantaneous motion can thus be in either direction, and switches between the
directions of travel can be frequent, cells can nonetheless control the average (“net”)
direction of transport. The physical mechanism underlying switches in direction remains
an open question, and may be different for different classes of cargos. However, two
general classes of mechanisms have been proposed. The first is a ‘coordination’
mechanism, where a protein or group of proteins controls the activity of the sets of
motors, controlling switching by turning one set of motors ‘off’ and other set ‘on’. In
contrast, a competing model suggests that no such regulatory complex exists, but rather,
that the plus-end and minus-end motors engage in a stochastic unregulated ‘tug-of-war’,
and that the overall motion of the cargos can simply be explained as an outcome of this
tug-of-war. This tug-of-war model was originally proposed theoretically to explain lipiddroplet motion. Using a combination of theory and in vitro & in vivo experiments, we
critically evaluate the tug-of-war model with regard to lipid droplet motion.