Involvement of gelsolin in cadmium-induced disruption of the mesangial cell cytoskeleton.
Cadmium (Cd2+) is known to cause a selective disruption of the filamentous actin cytoskeleton in the smooth muscle-like renal mesangial cell. We examined the effect of Cd2+ on the distribution of the actin-severing protein, gelsolin. Over 8 h, CdCl2 (10 microM) caused a progressive shift of gelsolin from a diffuse perinuclear and cytoplasmic distribution to a pattern decorating F-actin filaments. Over this time filaments were decreased in number in many cells, and membrane ruffling was initiated. Western blotting and 125I-F-actin gel overlays demonstrated an increase in actin-binding gelsolin activity in the cytoskeletal fraction of cell extracts following Cd2+ treatment. In in vitro polymerization assays, gelsolin acted as a nucleating factor and increased the rate of polymerization. Cytosolic extracts also increased the polymerization rate. Addition of Cd2+ together with gelsolin further increased the rate of polymerization. Gelsolin enhanced depolymerization of purified actin, and Cd2+ partially suppressed this effect. However, cytoskeletal extracts from Cd2+-treated cells also markedly increased depolymerization, suggesting further that Cd2+ may activate cellular component(s) such as gelsolin for actin binding. We conclude that a major effect of Cd2+ on the mesangial cell cytoskeleton is manifest through activating the association of gelsolin with actin, with gelsolin's severing properties predominating under conditions found in Cd2+-treated cells.
Apostolova
Margarita D
MD
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M5S 1A8, Canada.
Christova
Tania
T
Templeton
Douglas M
DM
D000818:Animals; D015153:Blotting, Western; D019256:Cadmium Chloride / Q000633:toxicity*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D018260:Gelsolin / Q000378:metabolism*; D007150:Immunohistochemistry; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D004785:Environmental Pollutants; D018260:Gelsolin; D019256:Cadmium Chloride