Membrane recruitment of Rac1 triggers phagocytosis

Rac1 is a Rho-family GTP-binding protein that controls lamellipodia formati on and membrane ruffling in fibroblasts. Recently, Rad and Cdc42, another m ember of the Rho-family, have been shown to regulate Fc receptor-mediated p hagocytosis in macrophages by controlling different steps of membrane and a ctin dynamics leading to particle engulfment. Here, me investigated the fun ction of Rad using a membrane recruitment system that mimics phagocytosis. Recruitment of an activated Rad protein to the cytoplasmic domain of an eng ineered membrane receptor by using rapamycin as a bridge induces ingestion of latex: beads bound to the receptor. Rad-mediated bead uptake depends on actin polymerisation since actin filaments accumulate at the bead/membrane binding sites and internalisation is inhibited by cytochalasin D. Internali sation is also abolished upon substitution of Phe37 to Leu in the Rad effec tor region. Our results indicate that by promoting actin polymerisation at particle attachment sites, Rad by acting through specific downstream effect ers induces plasma membrane remodeling that allows particle internalisation in a membrane-enclosed phagosome.