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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807939 | PMC |
| http://dx.doi.org/10.1016/j.biocel.2008.08.014 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
ADAMTS-1 and syndecan-4 intersect in the regulation of cell migration and angiogenesis.
J Cell Sci
April 2020
Faculty of Medicine and Health Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK
ADAMTS-1 is an extracellular protease with critical roles in organogenesis and angiogenesis. Here we demonstrate a functional convergence of ADAMTS-1 and the transmembrane heparan sulfate proteoglycan syndecan-4 in influencing adhesion, migration and angiogenesis. Knockdown of ADAMTS-1 in endothelial cells resulted in a parallel reduction in cell surface syndecan-4, attributable to increased matrix metalloproteinase-9 (MMP9) activity.
View Article and Find Full Text PDFShedding of syndecan-4 promotes immune cell recruitment and mitigates cardiac dysfunction after lipopolysaccharide challenge in mice.
J Mol Cell Cardiol
November 2015
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway; KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, Oslo, Norway; Department of Genetics, Harvard Medical School, Boston MA, USA.
Inflammation is central to heart failure progression. Innate immune signaling increases expression of the transmembrane proteoglycan syndecan-4 in cardiac myocytes and fibroblasts, followed by shedding of its ectodomain. Circulating shed syndecan-4 is increased in heart failure patients, however the pathophysiological and molecular consequences associated with syndecan-4 shedding remain poorly understood.
View Article and Find Full Text PDFMetalloproteinase-dependent and -independent processes contribute to inhibition of breast cancer cell migration, angiogenesis and liver metastasis by a disintegrin and metalloproteinase with thrombospondin motifs-15.
Int J Cancer
February 2015
School of Biological Sciences, Biomedical Research Centre, University of East Anglia, Norwich Research Park, Norwich, United Kingdom.
The ADAMTS proteinases are a family of secreted, matrix-associated enzymes that have diverse roles in the regulation of tissue organization and vascular homeostasis. Several of the 19 human family members have been identified as having either tumor promoting or suppressing roles. We previously demonstrated that decreased ADAMTS15 expression correlated with a worse clinical outcome in mammary carcinoma (e.
View Article and Find Full Text PDFPatterns of mRNA and protein expression during minus-lens compensation and recovery in tree shrew sclera.
Mol Vis
April 2011
Department of Vision Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-4390, USA.
Purpose: To increase our understanding of the mechanisms that remodel the sclera during the development of lens-induced myopia, when the sclera responds to putative "go" signals of retinal origin, and during recovery from lens-induced myopia, when the sclera responds to retinally-derived "stop" signals.
Methods: Seven groups of tree shrews were used to examine mRNA levels during minus lens compensation and recovery. Starting 24 days after eye opening (days of visual experience [VE]) lens compensation animals wore a monocular -5D lens for 1, 4, or 11 days.
Cleavage of syndecan-4 by ADAMTS1 provokes defects in adhesion.
Int J Biochem Cell Biol
April 2009
Medical Oncology Research Program, Vall d'Hebron University Hospital Research Institute/Universidad Autónoma de Barcelona, Barcelona 08035, Spain.
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.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!