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BMS Special Seminar: Microtubule severing by Spastin, Professor Joe Howard, Yale University

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Location: GLT3, Warwick Medical School

Abstract: The remodelling of the microtubule cytoskeleton underlies dynamic cellular processes, such as mitosis, ciliogenesis, and neuronal morphogenesis. An important class of microtubule remodellers are the severases—spastin, katanin, and fidgetin—which cut microtubules into shorter fragments. While severing activity might be expected to break down the microtubule cytoskeleton, inhibiting these enzymes in vivo actually decreases, rather increases, the number of microtubules, suggesting that severases have a nucleation-like activity. To resolve this paradox, we reconstituted Drosophila spastin in a dynamic microtubule assay and discovered that it is a dual-function enzyme. In addition to its ATP-dependent severing activity, spastin is an ATP-independent regulator of microtubule dynamics that promotes regrowth of microtubules by slowing shrinkage and increasing rescue. Mathematical modelling shows that the activities are necessary and sufficient to increase microtubule mass and thereby account for spastin’s in vivo phenotypes.

Biographj_howard.pngy: Jonathon (Joe) Howard is best known for his research on motor proteins and the cytoskeleton, and the development of techniques for observing and manipulating individual biological molecules. His research interests in the mechanics of cells and molecules include the sensation of force by receptor cells in the ear and skin, the segregation of the chromosomes during mitosis, the motility of cilia and flagella, and the branching morphogenesis of neurons. Brought up in Australia, where he studied mathematics and neurobiology at the Australian National University, he was professor of Physiology at the University of Washington in Seattle and a Director of the Max Planck Institute of Molecular Cell Biology & Genetics in Dresden, Germany before joining the faculty at Yale.

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