Document Detail


Gelsolin mediates collagen phagocytosis through a rac-dependent step.
MedLine Citation:
PMID:  14617805     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Pamela D Arora; Michael Glogauer; Andras Kapus; David J Kwiatkowski; Christopher A McCulloch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-11-14
Journal Detail:
Title:  Molecular biology of the cell     Volume:  15     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-29     Completed Date:  2004-10-27     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  588-99     Citation Subset:  IM    
Affiliation:
Canadian Institutes of Health Research Group in Matrix Dynamics, University of Toronto, Toronto, Ontario, Canada M5S 3E2.
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MeSH Terms
Descriptor/Qualifier:
Actin Cytoskeleton / metabolism*
Animals
Calcium / metabolism
Cells, Cultured
Collagen / metabolism*
Enzyme Activation / physiology
Fibroblasts / metabolism*
Gelsolin / metabolism*
Integrin alpha2beta1 / metabolism
Mice
Mice, Knockout
Microscopy, Confocal
Phagocytosis / physiology
Protein-Serine-Threonine Kinases / metabolism*
Proto-Oncogene Proteins c-akt
Chemical
Reg. No./Substance:
0/Gelsolin; 0/Integrin alpha2beta1; 7440-70-2/Calcium; 9007-34-5/Collagen; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
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