The mechanisms of action of the "catastrophe kinesins": Kinesins that destabilize the ends of microtubules

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The present research proposal is concerned with the mechanisms of action of a sub-family of the kinesins, the so-called "catastrophe-kinesins" which destabilize the ends of microtubules. These kinesins are essential for controlling the length and distribution of microtubule populations, by binding to microtubule ends, but little is know of their mechanism of action. Our group and others have 1) Established assays which examine the structural changes of microtubule ends during the change between growing and shrinking. This work has lead to the concept of a structural cap stabilizing growing microtubules. 2) Shown that the length of a microtubule population is controlled by the opposing activity of XKCM1, a catastrophe kinesin, and XMAP215, a MAP which stabilizes microtubules. In unpublished work, we have further shown the two proteins can oppose each other in the regulation of the growth of pure tubulin. In this project we propose to a) Correlate the structure of the microtubule end with the activity of XKCM1, by cryoelectron microscopy. b) To investigate how the activity of XKCM1 is modulated by the activity of XMAP 215.