The goal is to understand how tissue interactions control differentiated cell behavior. Interactions between epithelial and stromal tissues within developing organs generate specific positional information that is recognized by receptors on the cell surface. This information is translated via the receptor into specific cell shape and function. The mechanisms of this translation remain to be understood. To explore the translation mechanisms, this project proposes to study a specific receptor present on the surface of select epithelia. This molecule is a cell surface proteoglycan; it may be best characterized as an anchor, as it potentially becomes incorporated into extracellular matrix via its external domain, is intercalated into the plasma membrane, and is co-localized at these sites with the internal cytoskeleton. In addition, it appears to be actively oriented by the epithelial cell to specific regions of the cell surface where it likely participates in the biogenesis of matrix and cytoskeletal organization.
The specific aims of this project are to compare the biochemistry and function of this proteoglycan in several epithelia to assess its potential roles, examine mechanisms leading to its polarized delivery and accumulation at the cell surface, and explore the means of its direct linkage to the cytoskeleton. A better understanding of the biology of this cell proteoglycan will provide information on how tissue interactions in developing organs control specific cell behavior. Elucidation of such mechanisms will lead to a better understanding and prevention of the abnormalities in cell behavior that lead to diseases and birth defects.
| 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 |
