View Program - 63rd Annual Drosophila Research Conference

Cell wound repair is essential to cope with daily wear and tear, especially when cells are fragile as a result of trauma or from disease conditions. The three main steps of wound repair are highly conserved among different organisms: rapid membrane resealing; dynamic cytoskeletal reorganization for wound closure; and cell cortex (membrane and underlying cytoskeleton) remodeling to restore the cell to its unwounded state. We recently found that Rab35 is required for the cell cortex remodeling phase following wound closure in the Drosophila cell wound repair model. Rab35, a member of Rab family GTPases, regulates membrane trafficking and cytoskeleton dynamics in many cellular processes such as cytokinesis. We find that Rab35 is recruited to wounds and its RNAi knockdown exhibits premature actomyosin ring disassembly. Interestingly, we find that Rab35 functions in this context through two different downstream pathways. One pathway involves Mical, an oxidation-reduction enzyme that binds and disassembles F-actin, and SelR, a methionine sulfoxide reduction enzyme that works as a counterpart to Mical. Both Mical and SelR are recruited to wounds and their RNAi knockdowns exhibit opposite phenotypes in actomyosin ring remodeling. The other pathway involves Septins, a family of GTP-binding proteins that form hetero-oligomeric structures at the cell cortex to regulate cytoskeleton. We find that all five Drosophila Septins are recruited to wounds with similar, but not identical, spatial and temporal patterns. Consistent with this, they exhibit different mutant phenotypes with respect to actin dynamics, suggesting that Septins have non-redundant and complex-independent functions during cell wound repair. We are currently investigating the coordination between these pathways needed for proper remodeling of the cell cortex upon wound closure.

Rab35 mediates two distinct pathways that regulate actin modification through Mical/SelR and actin remodeling through Septins during cell wound repair