糖心TV

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鈥檚 in vivo phenotypes.