RGD Reference Report - Involvement of gelsolin in cadmium-induced disruption of the mesangial cell cytoskeleton. - Rat Genome Database

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Involvement of gelsolin in cadmium-induced disruption of the mesangial cell cytoskeleton.

Authors: Apostolova, MD  Christova, T  Templeton, DM 
Citation: Apostolova MD, etal., Toxicol Sci. 2006 Feb;89(2):465-74. Epub 2005 Nov 9.
RGD ID: 1599859
Pubmed: PMID:16280379   (View Abstract at PubMed)
DOI: DOI:10.1093/toxsci/kfj035   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
actin polymerization or depolymerization  IDA 1599859 RGD 
cellular response to cadmium ion  IDA 1599859 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
actin cytoskeleton  IDA 1599859 RGD 
perinuclear region of cytoplasm  IDA 1599859 RGD 
ruffle  IDA 1599859 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
actin binding  IDA 1599859 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gsn  (gelsolin)


Additional Information