The syndecans are a family of cell surface heparan sulfate proteoglycans that participate in regulating cell behaviors including cell proliferation, cell migration and adhesion. Past studies suggest that these activities are largely dependent on syndecan heparan sulfate chains, while the role of the individual syndecan core proteins remains poorly understood. However, evidence is emerging that these proteins have specialized binding and signaling functions. The proposed work will examine the various binding interactions and signaling functions of the syndecan core protein domains. Studies will (i) employ a facile adhesion and spreading assay to document syndecan signaling and identify signaling domains in the core protein, (ii) use in vitro and in vivo assays to identify binding partners of the syndecan cytoplasmic domain and (iii) identify and characterize a receptor that binds to the extracellular protein domain of syndecan-4. Results will lead to a better understanding of epithelial morphogenesis and to the mechanisms that regulate tumor cell metastasis and invasion.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD021881-15
Application #
6125664
Study Section
Special Emphasis Panel (ZRG3-PC (01))
Program Officer
Klein, Steven
Project Start
1985-09-01
Project End
2003-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
15
Fiscal Year
2000
Total Cost
$214,773
Indirect Cost
Name
University of Wisconsin Madison
Department
Pathology
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
McQuade, Kyle J; Rapraeger, Alan C (2003) Syndecan-1 transmembrane and extracellular domains have unique and distinct roles in cell spreading. J Biol Chem 278:46607-15
Burbach, Brandon J; Friedl, Andreas; Mundhenke, Christoph et al. (2003) Syndecan-1 accumulates in lysosomes of poorly differentiated breast carcinoma cells. Matrix Biol 22:163-77
Beauvais, DeannaLee M; Rapraeger, Alan C (2003) Syndecan-1-mediated cell spreading requires signaling by alphavbeta3 integrins in human breast carcinoma cells. Exp Cell Res 286:219-32
Rapraeger, Alan C (2002) Heparan sulfate-growth factor interactions. Methods Cell Biol 69:83-109