Comparisons of CapG and gelsolin-null macrophages: demonstration of a unique role for CapG in receptor-mediated ruffling, phagocytosis, and vesicle rocketing

Citation
W. Witke et al., Comparisons of CapG and gelsolin-null macrophages: demonstration of a unique role for CapG in receptor-mediated ruffling, phagocytosis, and vesicle rocketing, J CELL BIOL, 154(4), 2001, pp. 775-784
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
154
Issue
4
Year of publication
2001
Pages
775 - 784
Database
ISI
SICI code
0021-9525(20010820)154:4<775:COCAGM>2.0.ZU;2-T
Abstract
Capping the barbed ends of actin filaments is a critical step for regulatin g actin-based motility in nonmuscle cells. The in vivo function of CapG, a calcium-sensitive barbed end capping protein and member of the gelsolin/vil lin 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 m arrow macrophages profoundly inhibits macrophage colony stimulating factor- stimulated ruffling; reintroduction of CapG protein by microinjection fully restores this function. CapG-null macrophages also demonstrate similar to 50% impairment of immunoglobulin G, and complement-opsonized phagocytosis a nd lanthanum-induced vesicle rocketing. These motile functions are not impa ired in gelsolin-null macrophages and no additive effects are observed in C apG/gelsolin double-null macrophages, establishing that CapG function is di stinct from, and does not overlap with, gelsolin in macrophages. Our observ ations indicate that CapG is required for receptor-mediated ruffling, and t hat it is a major functional component of macrophage phagocytosis. These pr imary effects on macrophage motile function suggest that CapG may be a usef ul target for the regulation of macrophage-mediated inflammatory responses.