Comparisons of CapG and gelsolin-null macrophages: demonstration of a unique role for CapG in receptor-mediated ruffling, phagocytosis, and vesicle rocketing.
Capping the barbed ends of actin filaments is a critical step for regulating actin-based motility in nonmuscle cells. The in vivo function of CapG, a calcium-sensitive barbed end capping protein and member of the gelsolin/villin family, has been assessed using a null Capg allele engineered into mice. Both CapG-null mice and CapG/gelsolin double-null mice appear normal and have no gross functional abnormalities. However, the loss of CapG in bone marrow macrophages profoundly inhibits macrophage colony stimulating factor-stimulated ruffling; reintroduction of CapG protein by microinjection fully restores this function. CapG-null macrophages also demonstrate approximately 50% impairment of immunoglobulin G, and complement-opsonized phagocytosis and lanthanum-induced vesicle rocketing. These motile functions are not impaired in gelsolin-null macrophages and no additive effects are observed in CapG/gelsolin double-null macrophages, establishing that CapG function is distinct from, and does not overlap with, gelsolin in macrophages. Our observations indicate that CapG is required for receptor-mediated ruffling, and that it is a major functional component of macrophage phagocytosis. These primary effects on macrophage motile function suggest that CapG may be a useful target for the regulation of macrophage-mediated inflammatory responses.
Witke
W
W
Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Li
W
W
Kwiatkowski
D J
DJ
Southwick
F S
FS
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D018260:Gelsolin / Q000235:genetics*; D007425:Intracellular Membranes / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D009504:Neutrophils / Q000166:cytology / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics*; D010587:Phagocytosis / Q000502:physiology
D000199:Actins; D018260:Gelsolin; D008840:Microfilament Proteins; D009687:Nuclear Proteins; C483826:Capg protein, mouse