Calling the Shots: Prostaglandins Temporally Regulate Actin Remodeling During Drosophila Oogenesis. Tina L. Tootle, Andrew J. Spracklen, Xiang Chen. Anatomy and Cell Biology, University of Iowa, Carver College of Medicine, Iowa City, IA.

   The actin cytoskeleton is spatially and temporally regulated during both development and adult homeostasis. Temporal misregulation of actin remodeling directly contributes to the development and progression of multiple cardiovascular diseases, including developmental defects, heart attack, stroke, and cardiomyopathies. In the case of heart attack and stroke, such misregulation results in aberrant platelet activation and aggregation, resulting in vessel occlusion. Platelet activity is regulated by the opposing actions of prostaglandins (PGs), lipid signals. Thus it is critical for human health to understand the mechanisms by which PGs temporally regulate actin remodeling. Towards this goal we have established Drosophila oogenesis as a model for studying PG-dependent actin remodeling. PGs are required to prevent premature actin remodeling, as the loss of PG synthesis results in early, aberrant actin filament and/or aggregate formation (stage 9). We are taking advantage of this misregulation of actin remodeling to identify actin binding proteins that tightly control the onset of actin remodeling downstream of PG signaling. Specifically, we are using immunofluorescence to identify factors that co-localize to these aberrant, early actin structures and genetic interaction studies to identify factors that suppress or enhance their formation. We have found that Enabled, an actin elongation and anti-capping factor, localizes to the aggregates. Current efforts are focused on determining the signaling cascade by which PGs regulate Enabled activity to prevent premature actin remodeling. By combining correlative microscopy with robust genetic analysis, we can begin to determine how PG signaling temporally regulates actin cytoskeletal remodeling. Understanding the molecular mechanisms by which PGs temporally regulate actin remodeling during Drosophila oogenesis will provide insight into the conserved mechanisms by which PG signaling temporally regulates the actin cytoskeleton during human development and homeostasis, including events contributing to cardiovascular disease.