Stephanie Nowotarski  2007-present    
Ph.D. Student in Biology

Exploring Enabled & Capping Protein's Roles in Regulation of the Actin Cytoskeleton in
Drosophila Development
  Rearrangement of the actin cytoskeleton mediates changes in cell shape, migration and subsequently cell behavior during morphogenesis, wound healing and homeostasis of adult tissue. This regulation is facilitated by an array of proteins that function in actin nucleation, polymerization, capping, bundling and severing. The decision to continue filament elongation or to terminate is a critical decision in the context of the cell. Capping protein (CP) binds to the actin barbed end to terminate elongation, while the Enabled (Ena)/VASP family proteins function antagonistically, acting at barbed ends to promote continued elongation. We previously analyzed the role of Ena during embryogenesis revealing that Ena plays a role in subset of morphogenetic processes: germ band retraction, segment groove formation, head involution, and dorsal closure.

EnaGFP localization at leading edge and filopodia during
dorsal closure

You can see the movie at this link
Work in mammalian cell culture has provided support for an antagonistic relationship between CP and Ena/VASP. We are currently extending this analysis, teasing apart the antagonistic relationship between CP and Ena by studying its affect on dynamic actin during oogenesis. We are also starting toexplore how Ena's multi-domain structure affects its function. Studies of motility of cultured cells of the intracellular bacterium Listeria revealed that the EVH2 domain is sufficient for motility and anticapping function. The EVH1 domain is required for localization to sites of active actin turnover, while a proline rich domain is known to bind profilin. This data suggests that different Ena domains may be responsible for different morphogenetic processes in Drosophila. We are currently testing this hypothesis.

Publications

J-Y. Lin, W.J. Lin, W.-H. Hong, W.-C. Hung, S.H. Nowotarski, S. Montenegro Gouveia, I, Cristo and K.-H.Lin (2011) Morphology and organization of tissue cells in 3D microenvironment of monodisperse foam scaffolds. Soft Matter, in press. [Product of the Woods Hole Physiology Course!]

Gates, J., ,Nowotarski,S.H., Yin, H., Mahaffey, J.P., Bridges, T., Herrera,C., Homem,C.C.F., Janody, F., Montell, D.J.and Peifer,M. (2009) Enabled and Capping protein play important roles in shaping cell behavior during Drosophila oogenesis. Developmental Biology 333, 90-107.

Stevens, T L., Rogers, E M., Koontz, L. M. , Fox, D. T., Homem, C. C.F., Nowotarski, S. H., Artabazon, N. B., and Peifer, M. (2008). Using Bcr-Abl to examine mechanisms by which Abl kinase regulates morphogenesis in Drosophila. Molecular Biology of the Cell 19, 378-393.