Gelsolin Mediates Collagen Phagocytosis through a Rac-dependent Step

AUTOR(ES)

Arora, Pamela D.

FONTE

The American Society for Cell Biology

RESUMO

The role of gelsolin, a calcium-dependent actin-severing protein, in mediating collagen phagocytosis, is not defined. We examined α2β1 integrin-mediated phagocytosis in fibroblasts from wild-type (WT) and gelsolin knockout (Gsn-) mice. After initial contact with collagen beads, collagen binding and internalization were 60% lower in Gsn- than WT cells. This deficiency was restored by transfection with gelsolin or with β1 integrin-activating antibodies. WT cells showed robust rac activation and increased [Ca2+]i during early contact with collagen beads, but Gsn- cells showed very limited responses. Transfected gelsolin in Gsn- cells restored rac activation after collagen binding. Transfection of Gsn- cells with active rac increased collagen binding to WT levels. Chelation of intracellular calcium inhibited collagen binding and rac activation, whereas calcium ionophore induced rac activation in WT and Gsn- cells. We conclude that the ability of gelsolin to remodel actin filaments is important for collagen-induced calcium entry; calcium in turn is required for rac activation, which subsequently enhances collagen binding to unoccupied α2β1 integrins.

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