Microtubules are dynamic cytoskeletal filaments with important cellular functions, ranging from maintaining cellular structure to ensuring errorless cell division. Microtubules can grow and shorten by adding or losing tubulin subunits at their ends, these processes are coupled to binding and hydrolysis of GTP by tubulin. Microtubules switch between growing and shortening states stochastically; however, during cell division microtubule ends that interact with chromosomes via kinetochore proteins are synchronised in their dynamics. To understand the biochemical and structural mechanisms that allow kinetochores to control microtubule dynamics, we reconstitute their interactions in vitro using purified components and perform single-molecule fluorescence microscopy to understand dynamics of microtubule ends, as well as electron cryo-tomography to resolve the structures of microtubule ends and of proteins binding to them in different dynamics states. In my talk I will discuss our recent findings revealing the mechanisms that define growing and shortening states of isolated microtubules. I will also describe our observations connecting oligomerisation of the microtubule-binding outer kinetochore complexes Ndc80 and Ska to their ability to stabilise microtubule ends against shortening.

東京大学大学院理学系研究科・生物科学専攻・1分子遺伝学研究室