Cleavage of syndecan-4 by ADAMTS1 provokes defects in adhesion

Syndecan-4 is a membrane-bound heparan sulfate proteoglycan that participates in cell–cell and cell–matrix interactions and modulates adhesion and migration of many cell types. Through its extracellular domain, syndecan-4 cooperates with adhesion molecules and binds matrix components relevant for ce...

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Bibliographic Details
Published in:The international journal of biochemistry & cell biology 2009-04, Vol.41 (4), p.800-810
Main Authors: Rodríguez-Manzaneque, Juan Carlos, Carpizo, Darren, Plaza-Calonge, María del Carmen, Torres-Collado, Antoni Xavier, Thai, Shelley N.-M., Simons, Michael, Horowitz, Arie, Iruela-Arispe, M. Luisa
Format: Article
Language:English
Subjects:
Actins - metabolism
ADAM Proteins - metabolism
ADAMTS1 Protein
ADAMTS4 Protein
Animals
Binding Sites
Cell Adhesion - physiology
Cell Line
Cell Movement - physiology
CHO Cells
Cricetinae
Cricetulus
Endothelial cell
Extracellular proteolysis
Focal Adhesions - metabolism
Glycosaminoglycans - metabolism
Membrane Glycoproteins - metabolism
Metalloprotease
Metalloproteases - genetics
Metalloproteases - metabolism
Mice
Procollagen N-Endopeptidase - metabolism
Proteoglycan
Proteoglycans - metabolism
Syndecan-4 - metabolism
Transfection
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Summary:Syndecan-4 is a membrane-bound heparan sulfate proteoglycan that participates in cell–cell and cell–matrix interactions and modulates adhesion and migration of many cell types. Through its extracellular domain, syndecan-4 cooperates with adhesion molecules and binds matrix components relevant for cell migration. Importantly, syndecan-4 is a substrate of extracellular proteases, however the biological significance of this cleavage has not been elucidated. Here, we show that the secreted metalloprotease ADAMTS1, involved in angiogenesis and inflammatory processes, cleaves the ectodomain of syndecan-4. We further showed that this cleavage results in altered distribution of cytoskeleton components, functional loss of adhesion, and gain of migratory capacities. Using syndecan-4 null cells, we observed that ADAMTS1 proteolytic action mimics the outcome of genetic deletion of this proteoglycan with regards to focal adhesion. Our findings suggest that the shedding of syndecan-4 by ADAMTS1 disrupts cell adhesion and promotes cell migration.
ISSN:1357-2725
1878-5875
DOI:10.1016/j.biocel.2008.08.014