A Kinesin-Related Protein Required for the Mitotic Spindle Assembly

Mitosis is the process by which cells faithfully segregate their genetic material. This process is carried out by the mitotic spindle, which consists of a dynamic array of microtubules responsible for distributing replicated chromatids to each daughter cell. This proposal focuses on XKCM1, a kinesin-related protein required for mitotic spindle assembly in vitro. Our previous results indicated that XKCM1 acts by controlling the polymerization dynamics of microtubules which are necessary for spindle assembly. We have carried out a detailed mechanistic biochemistry study which showed that XKCM1 acts by binding to microtubules, causing a conformational change of the microtubule that results in microtubule depolymerization. This was a very novel and unexpected finding and has strong implications in understanding the biochemical mechanisms of this class of protein as well as understanding the role of microtubule dynamics in cellular function. We have shown that inhibition of a specific pool of XKCM1, that which is bound to kinetochores, causes a misalignment of chromosomes on the spindle. This data provides the first molecular handle on a protein that can couple microtubule dynamics to chromosome movement. The analysis of its function in live cells will be an important area of future research.