The microtubule cytoskeleton of a cell is not static but changes over time. Hence, the cell has to provide mechanisms to remodel microtubules. The dynamics of microtubules is mainly determined by the kinetics of subunit addition and removal at the ends. However, katanin and spastin are proteins that are able to sever microtubules internally.
Both enzymes belong to the large family of AAA proteins, use free enthaly from ATP hydrolysis, and fulfil their job as hexameric ring assemblies (as many AAA proteins). We recently found that the subunits in spastin rings are kinetically coupled, explaining why mutations have severe effects even in heterozygous patients (who still possess one intact copy of the gene). Curiously, kinetic assays show a strong co-operativiy of two (and not six) subunits.
We are currently setting up assays to study the mechanism by bio-mechanical assays in order to understand how the ATP turnover is coupled to the mechanical action. The severing process is thought to involve the removal of tubulin dimers from the microtubule lattice, possibly by pulling forces on the tubulin polypeptide. This, however, has not been shown so far. Furthermore, the removal of one dimer from the lattice is unlikely to lead to severing. We are addressing these questions by biophysical experiments.