Macrophages play a key role in inflammatory diseases, yet the mechanisms driving their recruitment to inflamed sites remain only partially understood. Our research focuses on complement C5a-mediated macrophage chemotaxis, integrating findings from knockout mouse models and existing literature. We highlight key regulators of cytoskeletal dynamics, including Rho GTPases, RhoGEFs (guanine nucleotide exchange factors), RhoGAPs (GTPase-activating proteins), myosins, actin NPFs (nucleation promoting factors), and actin nucleators. Using real-time chemotaxis assays, among other experimental approaches, we investigate how specific gene deletions affect macrophage cell polarization, motility, and chemotaxis.

We have also developed real-time imaging assays and used various knockout mouse models to explore the mechanism and signaling pathways of Fc receptor- and complement receptor-mediated phagocytosis. Similar to cell motility and chemotaxis, phagocytosis involves the coordinated local assembly and disassembly of actin filament-based structures.

Myosins are a superfamily of actin-dependent motor proteins, encoded by 36 genes in humans and mice, divided into 12 classes, including conventional class 2 myosins and unconventional myosins. The class 18 myosins include Myo18A and Myo18B. We recently identified a striated muscle-specific isoform of Myo18A, which we denoted Myo18A-gamma, that localizes to sarcomeric A-bands, similar to Myo18B. The other isoforms, Myo18A-alpha and Myo18A-beta, are widely expressed. We found that deleting Myo18a specifically in cardiac myocytes is embryonic lethal in mice, suggesting that loss of the gamma-isoform is responsible for the lethality of global deletion of Myo18a. To better understand the roles of the various Myo18A isoforms, we are generating and screening isoform-specific Myo18A knockout mouse models. Additionally, we are using cultured cardiac myocytes to explore the roles of class 18 myosins.