
Dorothy Schafer
Education
- B.S., SUNY College of Environmental Science & Forestry, 1977
- Ph.D., University of Michigan, 1983
Research Interests
Cells assemble a spectrum of interdependent F-actin networks that, together, move cells and organelles, establish polarity, confer mechanical properties and organize cells in tissues. Our research investigates the mechanisms by which cellular actin filaments assemble types of distinct networks that function in a coordinated manner. Two well-characterized actin networks are: 1) sheet-like, dendritic networks that power propulsive events as cells extend membrane and migrate and 2) contractile actomyosin networks that generate tension and pulling forces. Dendritic actin networks and actomyosin networks are often situated in close proximity in cells, yet, how these two very different networks form and function in a coordinated manner to maintain a dynamic, but coherent, global cytoskeleton is unknown.
We discovered that the large GTPase, dynamin2, is a component of dendritic actin networks where it influenced the assembly of actomyosin networks situated several microns away. Within lamellipodia, dynamin2 influenced the spatiotemporal distribution of actinin, an actin filament cross linker present in both dendritic actin networks and actomyosin. In cells, dynamin2 promotes formation of nascent actomyosin structures and their interactions at focal adhesions. In biochemical experiments, dynamin2, together with a binding partner, cortactin, bundled actin filaments and remodeled them in the presence of GTP. Taken together, our data support a hypothesis in which GTP hydrolysis by dynamin2 defines where and when dendritic actin filaments become crosslinked to generate bundled filament networks, such as nascent actomyosin. We are testing this hypothesis using quantitative imaging of living cells and robust biochemical analyses to identify the molecular mechanisms. We predict that dynamin2-mediated actin filament remodeling and crosslinking is a general mechanism by which actomyosin networks can be generated. Because actomyosin functions over long and short length scales, an ability of dynamin2 to influence actin networks locally and globally likely underlie its function in several cellular processes, such as migration, formation of cell-cell junctions, podosome dynamics, phagocytosis, exocytosis and cell-cell fusion.
Representative Publications
- Menon, M., Askinazi, O.L. and Schafer, D.A. (2014). Dynamin2 remodels lamellipodial actin networks to orchestrate lamellar actomyosin. PLoS ONE 9: e94330. PMCID: 3978067.
- Mooren, O.L., Kotova, T.I. and Schafer, D.A. (2009). Dynamin2 GTPase and cortactin remodel actin filaments. J. Biol. Chem., 284:23995 PMC2781994.
- Schafer, D.A., Weed, S.A., Binns, D., Karginov, A.V., Parsons, J.T. and Cooper, J.A. (2002). Dynamin2 and cortactin regulate actin assembly and filament organization. Curr. Biol., 12:1852.
- Lu, Q., Schafer, D.A. and Adler, P. (2015). The Drosophila planar polarity gene multiple wing hairs (mwh) directly regulates the actin cytoskeleton. Development, 142:2478 PMID: 26153232.
- Edwards, M., McConnell, P., Schafer, D.A. and Cooper, J.A. (2015). Regulation of capping protein is essential for function in cells. Nature Comm., 6:8415 PMC4598739.
- Pasic, L., Kotova, T.I., and Schafer, D.A. (2008). Ena/VASP proteins capture actin filament barbed ends. J. Biol. Chem., 283:9841 PMC2442276.