Microtubule Severing Enzymes

Microtubule severing enzymes are a novel class of microtubule-associated protein that can sever, or cut, microtubules anywhere along their length. Severing activity is vital for correct cell morphology and development during mitosis, neuronal development and maintenance, plant cell cellulose deposition, and maintaining motile cilia and flagella. For a recent commentary about the roles of severing enzymes in these important biological processes please see: D.J. Sharp and J.L. Ross, “Microtubule Severing Enzymes at the Cutting Edge,” Journal of Cell Science, (2012) web Sharp-JCS-2012.pdf.

We study the activities of severing enzymes one at a time using single molecule imaging techniques. We have discovered that katanin, the first severing enzyme identified and named after the Japanese Samurai sword, preferentially severs microtubules at lattice defect sites. J.D. Diaz-Valencia, M.M. Morelli, M. Bailey, D. Zhang, D.J. Sharp, and J.L. Ross, “Drosophila Katanin-60 Depolymerizes and Severs at Microtubule Defects,” Biophysical Journal, 100, 2440-2449 (2011). web Diaz-Valencia-BPJ-2011.pdf.

With our collaborator, Dr. David Sharp (Albert Einstein College of Medicine), we have discovered that katanin is responsible for maintaining the microtubule network at the cell cortex, and can depolymerize microtubules from their ends - preferentially from the microtubule plus-end. D. Zhang, K.D. Grode, S.F. Stewman, J.D. Diaz-Valencia, E. Liebling, U. Rath, T. Riera, J.D. Currie, D.W. Buster, A.B. Asenjo, H.J. Sosa, J.L. Ross, A. Ma, S.L. Rogers and D.J. Sharp “Drosophila katanin is a microtubule depolymerase that regulates cortical-microtubule plus-end interactions and cell migration,” Nature Cell Biology, 13, 361-369 (2011). web Zhang-NCB-2011.pdf

We have characterized a new severing enzyme, called fidgetin. Fidgetin knock-outs result in bone and cartilage deformities in mice and a head shaking phenotype because the inner ear canals are either too small or non-existent. David Sharp has characterized fidgeting in insect and human cells. We have characterized the biophysics and found that fidgetin can sever and depolymerize microtubule. Interestingly, fidgetin depolymerizes from the minus-end preferentially over the plus-end - making it very different from katanin. These cellular and in vitro results can be seen in our newest paper. S. Mukherjee, J.D. Diaz-Valencia, S. Stewman, S. Monnier, U. Rath, A.B. Asenjo, R.A. Charafeddine, H.J. Sosa, J.L. Ross, A. Ma and D.J. Sharp, “Human fidgetin is a microtubule severing enzyme and minus-end depolymerase that regulates mitosis,” Cell Cycle, 11, 1-8 (2012). web Mukerjee-CellCycle-2012.pdf