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Methods and Systems Developed for Characterization of Mammalian Katanin

Abstract

The katanin family of microtubule-severing enzymes present themselves as important characters in the story of cell homeostasis, division, proliferation, and migration. These enzymes are critical in promoting the microtubule density or stability required for the aforementioned functions. While it is well-known these enzymes function in the role of microtubule-severing, it is unclear why so many isoforms of A- and B- katanin exist in eukaryotes. The primary purpose of this work was to identify the redundancies, and/or specialized functions of the katanin superfamily using a series of knockout and rescue experimentation. The secondary purpose of this work was to clarify inter-subunit interactions, in particular those between AL2 and B1 katanin, as well as understand the structural and post-translational mechanisms of these enzymes. Developing a better understanding of how these enzymes function in the above cellular roles, as well as why there is a need for multiple isoforms with high sequence similarity in multiple mammalian species can promote the use of these proteins as diagnostic tools or use as targets for cancer and disease therapeutics.

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