Response gene to complement 32 promotes macrophage phagocytosis via activation of protein kinase C pathway [Immunology]

June 27th, 2014 by Tang, R., Zhang, G., Chen, S.-Y.

Macrophage phagocytosis plays an important role in host defense. The molecular mechanism especially factors regulating the phagocytosis, however, is not completely understood. In the present study, we found that response gene to complement 32 (RGC-32) is an important regulator of phagocytosis. Although RGC-32 is induced and abundantly expressed in macrophage during monocyte-macrophage differentiation, RGC-32 appears not to be important for this process because RGC-32 deficient bone marrow progenitor can normally differentiate to macrophage. However, both peritoneal macrophages and bone marrow-derived macrophages with RGC-32 deficiency exhibit significant defects in phagocytosis while RGC-32-overexpressed macrophages show increased phagocytosis. Mechanistically, RGC-32 is recruited to macrophage membrane where it interacts with F-actin to promote the formation of phagocytic cups. RGC-32 knockout impairs F-actin assembly and phagocytic cup formation. RGC-32 appears to interact with PKC to regulate PKC-induced phosphorylation of F-actin cross-linking protein Myristoylated alanine-rich C-kinase substrate. Taken together, our results demonstrate for the first time that RGC-32 is a novel membrane regulator for macrophage phagocytosis.