Syndecan-Regulated Receptor Signaling

The syndecans are transmembrane heparan sulfate (HS) proteoglycans expressed on all adherent cells (Bernfield et al., 1999; Rapraeger and Ott, 1998). A family of four, they have diverse functions ranging from participation in cell–cell adhesion, regulation of the signaling of HS binding growth factors, and organization of cell–matrix adhesion and signaling. A paper published in this issue of The Journal of Cell Biology (Iba et al., 2000) provides novel information on the specificity of syndecans in carrying out the latter function. The syndecan core proteins have several important domains, although much remains to be learned about their respective functions (Fig. 1; Bernfield et al., 1999; Rapraeger and Ott, 1998). The syndecans may function with several types of receptors. They are expressed at cell–cell adhesion sites (Fig. 2 A), e.g., syndecan-1 on epithelial cells and syndecan-2 in neuronal synapses. Here, they are expressed with the PDZ protein CASK and the cytoskeletal protein 4.1, and b -catenin linked to cadherins (Cohen et al., 1998; Hsueh and Sheng, 1999). All three of these cytoplasmic proteins have nuclear functions and CASK binding to syndecans has been shown recently to alter its nuclear targeting (Hsueh et al., 2000). This suggests that coregulation of cadherins and syndecans may have important outcomes in the nucleus. HS-binding growth factors (FGFs, VEGF, HGF, etc.) Address correspondence to Alan C. Rapraeger, Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 1300 University Avenue, Madison, WI 53706. Tel.: (608) 262-7577. Fax: (608) 2653301. E-mail: [email protected]