Mitotic kinesins in action: diffusive searching, directional switching, and ensemble coordination

Abstract

Mitotic spindle assembly requires the collective action of multiple microtubule motors that coordinate their activities in ensembles. However, despite significant advances in our understanding of mitotic kinesins at the single-motor level, multi-motor systems are challenging to reconstitute in vitro and thus less well understood. Recent findings highlighted in this perspective demonstrate how various properties of kinesin-5 and -14 motors-diffusive searching, directional switching, and multivalent interactions-allow them to achieve their physiological roles of cross-linking parallel microtubules and sliding antiparallel ones during cell division. Additionally, we highlight new experimental techniques that will help bridge the gap between in vitro biophysical studies and in vivo cell biology investigations and provide new insights into how specific single-molecule mechanisms generate complex cellular behaviors.

FIGURE 1:

Activities of kinesin-5 and kinesin-14 motors in isolation and in teams. (A) Individual kinesin-5 interacts with microtubules through one pair of heads with possible contribution of tail domains. Vertebrate kinesin-5 displays processive plus-end movement, but some fungal kinesin-5s display minus-end motility as single molecules. Teams of kinesin-5 slide antiparallel microtubules apart with plus-end directionality. (B) Individual kinesin-14 motors can diffuse along microtubules through either their head or microtubule-binding tail domains. In teams, kinesin-14s cross-link parallel bundles and slide apart antiparallel bundles through the action of the heads interacting with one filament and the tails interacting with the other filament.