Microtubule Dynamics

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Microtubules are biological polymers that alternate between periods of growth and shrinkage. This process, termed dynamic instability by its discovers Mitchison and Kirshner, is crucial for microtubule length regulation, for the exploration of intracellular space, and for cellular force generation. Despite its central role in cell biology, dynamic instability is poorly understood. For example, the GTP-cap, which is thought to regulate catastrophe, the transition from growth to shrinkage, has never been visualized on dynamic microtubules.

We are advancing the field by bringing three new approaches to the problem. First, we have developed assays to study microtubule dynamics using single-molecule techniques: total-internal reflection fluorescence microscopy (Brouhard et al. 2008, and see right for motors moving along a microtubule) and optical tweezers (Bormuth et al. 2009, Jannasch et al. 2013, Trushko et al. 2013). Second, we have used these assays to figure out how microtubule-associated proteins regulate microtubule dynamics. We have shown how depolymerizing kinesins target microtubule ends and couple ATP hydrolysis to microtubule shortening (Helenius et al. 2006, Varga et a. 2006, 2009, Friel and Howard 2011); we discovered that XMAP215 is a processive polymerase (Brouhard et al. 2008, Widlund et al. 2011); and we found that the end-binding protein EB1 recognizes the nucleotide state of tubulin (Zanic et al. 2009) to increase catastrophe and to synergize with XMAP215 to increase microtubule growth rates (Zanic et al. 2013). The third approach is to use theory to gain insight into microtubule length control (Varga et al. 2009), the catastrophe switch (Gardner et al. 2011, Bowne-Anderson et al. 2013) and the collective properties of motor proteins (Leduc et al. 2012).