Identification of the Molecular Determinants for Regulation of Microtubule Severing by Katanin

Microtubules are dynamic cytoskeletal polymers that form complex and highly organized arrays essential for cell motility, morphogenesis, and division. Microtubule severing is a reaction that generates an internal break in the microtubule polymer and catalysis of microtubule severing is important for the proper organization and function of microtubule-based arrays in a wide range of eukaryotic cells. Katanin is a conserved heterodimeric ATPase that severs and disassembles stable microtubules, but the molecular and cellular mechanisms underlying microtubule severing by katanin are poorly understood. Using cultured Drosophila cells as our model system, we conducted two independent studies to investigate 1) whether katanin plays a role in cell migration and 2) how the structural domains of katanin regulate microtubule severing. In our first study, we discovered that Drosophila katanin functions as a negative regulator of cell motility by suppressing fast and persistent migration. In our second study, we identified the non-catalytic domains of Drosophila katanin as the major determinants for regulation of its abundance and microtubule-disassembly activity. Taken together, our work contributes to a basic understanding about how cells regulate microtubule severing to build and remodel microtubule-based arrays necessary for normal cellular function.Doctor of Philosoph