Structural adaptation of kinesin-5 motors

Executive report

This research is focused on the bipolar kinesin-5 motor proteins that are among the essential elements mediating the dynamics of the microtubule (MT)—based mitotic spindle, by crosslinking and sliding apart antiparallel MTs within the mitotic spindle. Majority of kinesin-5 motors are plus—end directed. However, remarkably, two previous reports, one of them from our laboratory, have shown that Cin8, a Saccharomyces cerevisiae kinesin-5 motor, is bi—directional, i.e., it can move in the plus— and minus—end directions on the MTs and switch directionality under different experimental conditions. Subsequent studies, including one from our laboratory, reported that two other kinesin-5 homologs are bi- directional. Taken together, these reports suggest that the bi—directional motility of some kinesin-5 motors may be functionally important. However, the mechanism, regulation, and physiological role of this bi—directional motility are yet to be established. Moreover, since the bi—directional kinesin-5 motors reported thus far are from fungal cells, an important question regarding the structural evolutionary adaptation of kinesin-5 motors from lower and higher eukaryotes remained unanswered. The collaborative research by the US and Israeli Pls is aimed at addressing these questions.

The unique approach undertaken in our collaborative research relies on combining in vivo and in vitro assays to study the function and regulation of kinesin motor proteins. Since mitotic molecular motor proteins perform their intracellular function by binding and moving along MTs, this approach enables us to understand both the molecular mechanisms that enable bi—directional motility and the physiological importance of such motility. Following is the description of the main achievements of our research.