Published 20 August 2001. doi:10.1083/jcb.200101113
© The Rockefeller University Press,
0021-9525/2001/8/775 $5.00
The Journal of Cell Biology, Volume 154, Number 4, August 20, 2001 775-784
Comparisons of CapG and gelsolin-null macrophages
:
demonstration of a unique role for CapG in receptor-mediated ruffling, phagocytosis, and vesicle rocketing
Walter Witke1,
Wei Li2,
David J. Kwiatkowski1 and
Frederick S. Southwick2
1 Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115
2 Infectious Disease Division, Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32610
Address correspondence to David Kwiatkowski, Division of Experimental Medicine, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave., Boston, MA 02115. Tel.: (617) 278-0384. Fax: (617) 734-2248. E-mail: dkwiatkowski{at}rics.bwh.harvard.edu
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 factorstimulated ruffling; reintroduction of CapG protein by microinjection fully restores this function. CapG-null macrophages also demonstrate
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.
Key Words: CapG; gelsolin; macrophages; ruffling; phagocytosis

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