Common effects of attractive and repulsive signaling: Further analysis of Mical-mediated F-actin disassembly and regulation by Abl

Abstract

To change their size, shape, and connectivity, cells require actin and tubulin proteins to assemble together into long polymers – and numerous extracellular stimuli have now been identified that alter the assembly and organization of these cytoskeletal structures. Yet, there remains a lack of defined signaling pathways from the cell surface to the cytoskeleton for many of these extracellular signals, and so we still know little of how they exert their precise structural effects. These extracellular cues may be soluble or substrate-bound and have historically been classified into two independently acting and antagonistic groups: growth-promoting/attractants (inducing turning toward the source of the factor/positive chemotropism) or growth-preventing/repellents (turning away from the source of the factor/negative chemotropism). Paradoxically, our recent results directly link the action of growth factors/chemoattractants and their signaling pathways to the promotion of the disassembly of the F-actin cytoskeleton (a defined readout of repellents/repulsive signaling). Herein, we add to this by simply driving a constitutively active form of Mical, which strongly disassembles F-actin/remodels cells in vivo independent of repulsive cues – and find that loss of Abl, which mediates growth factor signaling in these cells, decreases Mical's F-actin disassembly/cellular remodeling effects. Thus, our results are consistent with a hypothesis that cues defined as positive effectors of movement (growth factors/chemoattractants) can at least in some contexts enhance the F-actin disassembly and remodeling activity of repellents.

Keywords

• Attraction
• Cytoskeleton
• Guidance Cues
• Kinase
• Oxidation
• Post-translational Modification
• Phosphorylation
• Repulsion
• Semaphorin
• Plexin