the-utility-stage-specific-mid-to-late-drosophila-follicle

The Utility of Stage-specific Mid-to-late <em>Drosophila</em> Follicle Isolation

Drosophila oogenesis or follicle development has been widely used to advance the understanding of complex developmental and cell biologic processes. This ...

University of Iowa Carver College of Medicine

Although prostaglandins (PGs)-lipid signals produced downstream of cyclooxygenase (COX) enzymes-regulate actin cytoskeletal dynamics, their mechanisms of action are unknown. We previously established Drosophila oogenesis, in particular nurse cell dumping, as a new model to determine how PGs regulate actin remodeling. PGs, and thus the Drosophila COX-like enzyme Pxt, are required for both the parallel actin filament bundle formation and the cortical actin strengthening required for dumping. Here we provide the first link between Fascin (Drosophila Singed, Sn), an actin-bundling protein, and PGs. Loss of either pxt or fascin results in similar actin defects. Fascin interacts, both pharmacologically and genetically, with PGs, as reduced Fascin levels enhance the effects of COX inhibition and synergize with reduced Pxt levels to cause both parallel bundle and cortical actin defects. Conversely, overexpression of Fascin in the germline suppresses the effects of COX inhibition and genetic loss of Pxt. These data lead to the conclusion that PGs regulate Fascin to control actin remodeling. This novel interaction has implications beyond Drosophila, as both PGs and Fascin-1, in mammalian systems, contribute to cancer cell migration and invasion.

Drosophila Fascin is a novel downstream target of prostaglandin signaling during actin remodeling.

While Prostaglandins (PGs), lipid signals produced downstream of cyclooxygenase (COX) enzymes, regulate actin dynamics in cell culture and platelets, their roles during development are largely unknown. Here we define a new role for Pxt, the Drosophila COX-like enzyme, in regulating the actin cytoskeleton-temporal restriction of actin remodeling during oogenesis. PGs are required for actin filament bundle formation during stage 10B (S10B). Additionally, loss of Pxt results in early actin remodeling, including extensive actin filaments and aggregates, within the posterior nurse cells of stage 9 (S9) follicles; wild-type follicles exhibit similar structures at a low frequency. Hu li tai shao (Hts), the homolog of Adducin, and Villin (Quail), an actin bundler, localize to all early actin structures, while Enabled (Ena), an actin elongation factor, preferentially localizes to those in pxt mutants. Reduced Ena levels strongly suppress early actin remodeling in pxt mutants. Furthermore, loss of Pxt results in reduced Ena localization to the sites of bundle formation during S10B. Together these data lead to the model that PGs temporally regulate actin remodeling during Drosophila oogenesis by controlling Ena localization/activity, such that in S9, PG signaling inhibits, while at S10B, it promotes Ena-dependent actin remodeling.

Article	Year
Drosophila Fascin is a novel downstream target of prostaglandin signaling during actin remodeling. Molecular biology of the cell\| PubMed ID: 23051736	2012
Prostaglandins temporally regulate cytoplasmic actin bundle formation during Drosophila oogenesis. Molecular biology of the cell\| PubMed ID: 24284900	2013

Andrew J. Spracklen

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