Diagrammatic representation of phosphoinositide metabolism and actin recruitment. (A) FcγR-mediated phagocytosis. (B) CR3-mediated phagocytosis. (A) During FcγR-mediated phagosome formation (top), phosphoinositide kinases transform phosphoinositide into PI(4,5)P₂ and PI(3,4,5)P₃ and regulate actin polymerization within the growing pseudopod. Although PI4K and PI3KI remain associated with the maturing FcγR-mediated phagosome (bottom), PIP5K detaches upon sealing, resulting in depletion of PI(4,5)P₂ and failure to accumulate PI(3,4,5)P₃. (B) CR3-mediated phagosome formation (top) mirrors FcγR-mediated phagosome formation in terms of PI(4,5)P₂ and PI(3,4,5)P₃ synthesis and actin polymerization. The 5′-phosphoinositide phosphatase Inpp5B likely contributes to hydrolyze PI(4,5)P₂ and PI(3,4,5)P₃ during phagosome sealing. Unlike FcγR-mediated phagosomes, CR3-mediated phagosomes (bottom) retain PIP5K after sealing, which allows de novo PI(4,5)P₂ and PI(3,4,5)P₃ synthesis and actin polymerization. Accumulation of PI(4,5)P₂ and PI(3,4,5)P₃ is possible because PI(3)P dislodges Inpp5B.