Dorothy A. Schafer, Ph.D.

Area:

Website:

Google:

Bio:

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.
(Show less)

Mean distance: (not calculated yet)