Disassembling F-actin Networks Through Manipulations of Mical and Actin Bundling Proteins. Jimok Yoon, Heng Wu, Jonathan Terman. Center for Basic Neuroscience, U.T.Southwestern Medical Center at Dallas, Dallas, TX.
Cells continually interact with their environment and change their morphology in response to extracellular cues. Semaphorins are one of the largest families of these extracellular guidance cues and play critical roles in neurobiology, immunology, cardiovascular health, and cancer. Semaphorins are best known for their ability to disassemble actin filaments (F-actin) and we recently found that Mical, a protein that directly associates with the Semaphorin cell-surface receptor Plexin, is a novel F-actin disassembly factor that mediates Semaphorin/Plexin F-actin rearrangements. Herein, we use genetic approaches in the Drosophila model system and in vitro actin biochemical approaches with purified proteins to further investigate Mical-mediated F-actin alterations. We find that Mical and F-actin stabilizing/bundling proteins such as fascin and espin play antagonistic roles in regulating the F-actin cytoskeleton during development in vivo. Consistent with our in vivo data, we find that purified Mical protein disassembles fascin and espin bundled actin filaments in vitro. Our results go on to support a hypothesis that Semaphorin/Plexin/Mical directly disassembles the F-actin cytoskeleton and by so doing, triggers other actin regulatory proteins to reorganize a more complex F-actin network.