Phagocytosis: A Fundamental Process in Immunity

Figure 6

Cytoskeleton changes during phagocytosis. (a) Phagocytes explore their surroundings for phagocytic targets by projecting membrane ruffles, filopodia, and podosomes. These membranes contain mostly linear actin fibers. (b) Upon recognition of a target particle, the actin cytoskeleton is disrupted at the phagocytic cup by the action of coronins (F-actin debranching proteins) and cofilin and gelsolin (F-actin-severing proteins). (c) As more phagocytic receptors get engaged around the particle, the cell extends pseudopodia, which contain new branched actin fibers. Actin nucleation and F-actin polymerization are mediated by the Arp2/3 protein complex, which can be stimulated by the GTPases Rac and Cdc42, via the nucleation-promoting factor Scar/WAVE. (d) At the last step, depolymerization of actin filaments from the base of the nascent phagosome may facilitate curving of the membrane around the particle and provide room for fusion of internal vesicles, a source of endomembranes. Actin depolymerization is controlled by phosphatidylinositol 3-kinase (PI3K), through its product phosphatidylinositol (3,4,5)-trisphosphate (PIP₃), which may recruit Rho GAPs that inactivate the GTPases Rac and Cdc42, thus reducing Arp2/3 activity. PIP₃ also recruits myosins, which provide contractile activity that facilitates phagosome closure. At the same time, phospholipase C (PLC) cleaves phosphatidylinositol (4,5)-bisphosphate (PIP₂) to generate diacylglycerol (DAG) and inositol-trisphosphate (IP₃). The reduction of PIP₂ will liberate cofilin and increase F-actin severing activity.