Action at a distance along the microtubule couples kinesin motorsMeredith D Betterton*

Currently, our ideas about biopolymers focus on mechanics. For example, the high flexibility of DNA enables looping to regulate gene expression. By contrast, rigid microtubules are thought of as structural elements and highways for traffic. However, a handful of new results suggest that microtubules undergo subtle structural changes that propagate along their length. Microtubules may therefore act as a coupling medium for interactions between proteins bound to them. In this work, modeling of motor-protein motion along microtubules predicted an unexpected long-range interaction. Experimental results confirmed that microtubules can physically couple motor movement in the absence of detectable short-range interactions. This occurs for the human kinesin-4 Kif4A, which contributes to the stability of antiparallel microtubule overlaps in the mitotic spindle. In a reconstituted system, Kif4A changes the run length and velocity of other motors on the same microtubule in the dilute binding limit, when approximately 10-nm-sized motors are much farther apart than the motor size. This effect does not depend on specific motor-motor interactions because similar changes in Kif4A motility are induced by kinesin-1 motors. A micrometer-scale attractive interaction potential between motors is sufficient to recreate the experimental results in our model. Unexpectedly, our theory suggests that long-range microtubule-mediated coupling affects not only binding kinetics but also motor mechanochemistry. Therefore, the model predicts that motors can sense and respond to motors bound several micrometers away on a microtubule. Our results are consistent with a paradigm in which long-range motor interactions along the microtubule enable additional forms of collective motor behavior, possibly due to changes in the microtubule lattice.