Role and regulation of the microtubule-severing enzyme Katanin

Microtubules (MTs) are dynamic cytoskeleton polymers, which play a central role in cell division, morphogenesis, motility and signaling. Most MT regulatory proteins interact with the plus or minus end of microtubules and thereby control their polymerization and depolymerization rates. However, one class of MT regulator interacts with the MT lattice and severs MTs throughout their length, thereby controlling their size and density in the cell. Three evolutionarily conserved MT-severing enzymes have been identified: Fidgetin, Spastin and Katanin. Mutations of these enzymes have been linked to various defects and pathologies including developmental defects and neurodegenerative disorders. However, little is known about the precise mechanisms by which these enzymes sever MTs. Likewise, how these enzymes are regulated in space and time is poorly understood. Combining biochemistry, genetic and live cell imaging, we are currently focusing on deciphering the mode of action and regulation of Katanin, which is essential for female meiotic spindle assembly in C. elegans.