Dynamics and Regulation of Microtubule Minus Ends
Strothman, Claire E
Dynamics and Regulation of Microtubule Minus Ends Microtubules are an integral part of the cytoskeletal system in cells and serve essential roles in cell division, intracellular transport, and morphogenesis. Microtubules are hollow filamentous structures composed of tubulin protein. Tubulin is a heterodimer which consists of an - and a -tubulin monomer. In the microtubule itself, tubulin dimers are arranged in a head-to-tail fashion, such that one end of the microtubule has -tubulin exposed, while the other has -tubulin exposed. These two ends are therefore biochemically and structurally distinct, and are respectively classified as the microtubule plus-end and minus-end. Both microtubule ends exhibit a behavior called dynamic instability, in which the end stochastically switches between phases of growth and shrinkage, through transitions called catastrophe and rescue. Microtubule network in cells is often radially-organized, with minus ends clustered centrally, and plus ends radiating outwards towards the cell periphery. These free plus ends are highly dynamic, while many of the minus ends are anchored to microtubule-organizing structures, and therefore thought to be non-dynamic. However, in many cellular contexts, including neurons, epithelial, and muscle cells, microtubule network is not radially-organized, and there are significant sub-populations of unanchored minus ends whose dynamics have to be actively regulated. Studies of microtubule dynamics to date have almost exclusively focused on more-dynamic and readily-observable microtubule plus ends. Based on the in vitro approaches with purified protein components it has been well known that minus ends exhibit distinct dynamic properties, but what mechanisms underlie these differences between the dynamics of the two ends was not known. This research addresses the fundamental mechanistic differences in dynamics between microtubule plus and minus ends, as well as the regulation of minus ends by the minus-end directed microtubule motor kinesin-14 HSET/KIFC1. By shedding the light on the dynamics of poorly-studied microtubule minus ends, this work provides important insight into the mechanisms of microtubule regulation, essential for microtubule function in cells.