Mitotic spindle assembly and function
Work in the Wadsworth laboratory is directed at understanding mitosis, the process by which the duplicated genetic material is accurately segregated into two new daughter cells. Understanding mitosis is important because errors in the process result in cells with the wrong number of chromosomes, a situation that is commonly found in cancer cells. Our overall goal is to understand basic cell biology of mitosis to provide insight into this fundamental process. Ongoing work is directed at understanding the mechanism by which the mitotic spindle self-assembles from component parts as cells prepare to divide and how mitotic motor proteins that are critical for this process are spatially and temporally regulated. Current projects include using gene depletion and replacement strategy in mammalian cells to investigation motor protein regulation during spindle formation. In a second project we are investigating conserved and divergent features of kinesin 5 motors using both budding yeast and mammalian cells. The simple spindle in yeast also allows us to quantify motor localization by microscopy. In a new project, we are examining mitosis in Naegleria amoeba, an emerging model system. This work, in collaboration with the Fritz-Laylin lab, seeks to understand cell division in this simple model.
Ma, N., Titus, J., Gable, A., Ross, J. L., Wadsworth, P. 2011. TPX2 regulates the localization and activity of Eg5 in the mammalian mitotic spindle . Journal of Cell Biology, 195: 87-98.
Gable, A., Qiu, M. , Titus, J. ,Balchand, S., Ferenz, N. P., Ma, N., Fagerstrom, C., Ross, J. L., Yang, G., Wadsworth, P. 2012. Dynamic reorganization of Eg5 in the mammalian spindle throughout mitosis requires dynein and TPX2. Molecular Biology of the Cell, 23: 1254-1266.
Ferenz, N., N. Ma, W.-L. Lee, and P. Wadsworth. 2010a. Imaging Protein Dynamics in Live Mitotic Cells. Methods, in press.
Ferenz, N.P., A. Gable, and P. Wadsworth. 2010b. Mitotic Functions of Kinesin-5. Seminars in Cell and Developmental Biology, 21: 255-259.
Ma, N., S. Tulu, N. Ferenz, C. Fagerstrom, A. Wilde, and P. Wadsworth. 2010. Poleward Transport of TPX2 in mammalian spindles requires Eg5, dynein and microtubule flux. Molecular Biology of the Cell, 21: 979-988.
Ferenz, N., R. Paul, C. Fagerstrom, A. Mogilner, and P. Wadsworth. 2009. Dynein antagonizes Eg5 by crosslinking and sliding antiparallel microtubules. Current Biology, 19: 1833-1838.
Murthy, K., and P. Wadsworth. 2008. Dual Role for Microtubules in Regulating Cortical Contractility during Cytokinesis. Journal of Cell Science, 121: 2350-2359.
Tulu, U.S., C. Fagerstrom, N.P. Ferenz, and P. Wadsworth. 2006. Molecular requirements for kinetochore-associated microtubule formation in mammalian cells. Current Biology, 16: 536-541.
Murthy, K., and P. Wadsworth. 2005. Myosin-II-dependent localization and dynamics of F-actin during cytokinesis. Current Biology, 15: 724-731.
Tulu, U.S., N. Rusan, and P. Wadsworth. 2003. Peripheral, non-centrosome-associated microtubules contribute to spindle formation in centrosome containing cells. Current Biology, 13: 1894-1899.
Landen, J.W., Lang, R., McMahon, S.J., Rusan, N., Yvon, A.C., Adams, A.W., Sorcinelli, M., Campbell, R., Bonaccorsi, P., Wadsworth, P. Archer, D.R., Ansel, J., Armstrong, C.A. and H. Joshi. 2002. The tubulin binding agent noscapine for the treatment of murine melanoma. Cancer Research, 62: 4109-4119.
Rusan, N., Tulu, U.S., Fagerstrom, C. and P. Wadsworth. 2002. Microtubule rearrangment in prophase/prometaphase cells requires cytoplasmic dynein. Journal of Cell Biology, 158: 997-1003.
Yvon, A.C., walker, J.W., Danowski, B.A., Fagerstrom, C., Khojakov, A. and P. Wadsworth. 2002. Centrosome reorientation in wound edge cells is cell type specific. Molecular Biology of the Cell, 13: 1871-1880.