Phagocytosis: A Fundamental Process in Immunity

Figure 3

Complement receptor signaling in phagocytosis. The complement receptor 3 (CR3 integrin) binds the complement fragment iC3b and initiates a signaling cascade that activates Rho, either independently of tyrosine kinases (in macrophages) or via Syk, which is recruited through an ITAM-bearing molecule (such as DAP12 or the Fc receptor γ chain). Syk may also activate the GEF Vav to further activate Rho. Rho, in turn, leads to actin polymerization via two mechanisms. Rho can activate Rho kinase (ROCK), which phosphorylates and activates myosin II, inducing accumulation of Arp2/3 and actin assembly at the phagocytic cup. Rho can also induce accumulation of mDia1 (mammalian diaphanous-related formin 1), which promotes actin polymerization. In addition, mDia1 binds directly to the microtubule-associated protein CLIP-170 providing a link to the microtubule cytoskeleton. P represents a phosphate group. ITAM, immunoreceptor tyrosine-based activation motif.