Gelsolin mediates collagen phagocytosis through a rac-dependent step |
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Authors: | Arora Pamela D Glogauer Michael Kapus Andras Kwiatkowski David J McCulloch Christopher A |
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Institution: | Canadian Institutes of Health Research Group in Matrix Dynamics, University of Toronto, Toronto, Ontario, Canada M5S 3E2. |
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Abstract: | The role of gelsolin, a calcium-dependent actin-severing protein, in mediating collagen phagocytosis, is not defined. We examined alpha 2 beta 1 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 beta1 integrin-activating antibodies. WT cells showed robust rac activation and increased Ca(2+)](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 alpha 2 beta 1 integrins. |
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