*3.3.1 Roles of small-GTP binding proteins in engulfment*

Pathogen recognition by scavenger and opsonin receptors initiates cytoskeleton remodeling, leading to pathogen engulfment. The regulatory signaling pathways rely on each receptor ligated to the particles, but all forms of engulfment require the recruitment of filamentous (F)-actin beneath tethered particles and subsequent rearrangement of F-actin. F-actin is primarily controlled by three small-GTP binding proteins, including Ras homolog (Rho) family member A (RhoA), Ras-related C3 botulinus toxin substrate 1 (Rac1), and cell division control protein 42 homolog (Cdc42), both of which are members of Rho family [2, 4]. The binding of particles to receptors causes RhoA, Rac1, and Cdc42 to be converted from the GDP-bound inactive form to active form and then recruited from the cytosol to the cell membrane under tethered particles, where they regulate F-actin rearrangement and subsequent

cell motility by triggering the formation of stress fibers, lamellipodia, and filopodia, respectively [2].

#### *3.3.2 Receptor-dependent roles of small-GTP binding proteins*

The roles of these small-GTP binding proteins have been systematically studied after the ligation of Fcγ receptors. FcγRIIA-transfected COS fibroblasts treated with IgG-opsonized particles facilitated recruitment of all the small-GTP binding proteins to the nascent F-actin phagocytic cup, whereas blocking Rac1 and Cdc42 suppressed engulfment by preventing the formation of membrane ruffles and filopodia, respectively; however, blocking RhoA had no effects on the engulfment [53]. In contrast, when CR3-transfected COS fibroblasts were treated with complement-opsonized particles, only RhoA colocalized with F-actin, and blocking RhoA compromised CR3 mediated phagocytosis [53]. Dectin-1 has downstream signaling cascades that are highly similar to those of Fcγ receptors [54]. Although the downstream pathways of MSR1 and CD36 have not yet been reported, a recent study indicated that the Gramnegative bacterium *Escherichia coli* interacts with MARCO, which activates Rac1 to initiate F-actin polymerization, filopodia formation, and subsequent engulfment in murine alveolar macrophages [55].
