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J. Exp. Med., Volume 187, Number 2, January 19, 1998 161-176

Functional Separation of Pseudopod Extension and Particle Internalization during Fcgamma Receptor-mediated Phagocytosis

By Malcolm B. Lowry,* Anne-Marie Duchemin,* John M. Robinson,Dagger and Clark L. Anderson*

From the * Department of Internal Medicine, and Dagger  Department of Cell Biology, Neurobiology, and Anatomy, The Ohio State University College of Medicine, Columbus, Ohio 43210

Receptors for the Fc portion of immunoglobulin (Ig)G (Fcgamma R) mediate phagocytosis of IgG-opsonized particles by a process that can be divided into four major steps: receptor-ligand binding, pseudopod extension, internalization, and lysosomal fusion. We have expressed single classes of Fcgamma R in COS fibroblasts to examine the structural determinants necessary to complete the four steps of phagocytosis. Using phase contrast, fluorescence, confocal, and electron microscopy we have demonstrated that Fcgamma R-expressing COS cells can phagocytose in a manner similar to that of professional phagocytes. We have further analyzed the capacity of the three classes of Fcgamma R to phagocytose, placing special emphasis on the Fcgamma RIA-gamma chain complex, which allowed us to examine independently the roles of the ligand-binding unit (Fcgamma RIA) and the signaling unit (gamma  chain). We found that receptor complexes containing a conserved tyrosine activation motif (ITAM), as found in the cytoplasmic domain of Fcgamma RIIA and in the gamma  chain associated with Fcgamma RIA and Fcgamma RIIIA, readily internalized target particles. In contrast, Fcgamma RIA alone, having no ITAM, was unable to internalize target particles efficiently, but did mediate pseudopod extension. Cotransfection of gamma  chain with Fcgamma RIA restored the ability of the receptor to internalize target particles. A mutant Fcgamma RIA in which the cytoplasmic domain had been deleted was also capable of mediating pseudopod extension, showing that neither the gamma  chain nor the cytoplasmic domain of Fcgamma RIA were required for this step. Cytochalasin D, an inhibitor of actin polymerization, blocked particle internalization by all Fcgamma R, but did not block pseudopod extension. Staining the Fcgamma RIA COS cells for F-actin and for tyrosine phosphoproteins, we found that actin did not polymerize during Fcgamma RIA-mediated pseudopod extension, nor were tyrosine kinases activated. Our data suggest that pseudopod extension and internalization are functionally distinct steps mediated through different pathways.


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