Syndecane

Syndecanes belong to a family of proteoglycans (transmembrane domain proteins) which are believed to act as co-receptors, especially for G-protein-coupled receptors (Carey D J 1997). The syndecane protein family consists of 4 members (syndecane 1 -4). Their "core proteins" are linked to 3-5 heparan sulfate and chondroitin sulfate chains, which in turn enable interaction with a variety of ligands. Thus with fibroblast growth factors, VEGF, TGF-beta, fibronectin and antithrombin-1. Interactions between fibronectin and some syndecans can be modulated by the extracellular matrix protein tenascin C.

All syndecanes have an N-terminal signal peptide, an ectodomain, a single hydrophobic transmembrane domain and a short C-terminal cytoplasmic domain. They are anchored to the plasma membrane via the 24 to 25 amino acid long hydrophobic transmembrane domains. Other proteoglycans bind on the cell surface via a glycosyl-phosphatidyl-inositol bond.

The functionality of syndecane is supported by glycosylaminoglycans that help to interact with various extracellular ligands. The following functionalities are associated with the activity of syndecanes:

Growth factor receptor activation: Glycosaminoglycans bound to syndecane help to bind the various growth factors to activate important cellular signalling mechanisms. Growth factors such as FGF2, HGF, EGF, VEGF, neuregulins and others interact with syndecanes (Bernfield M et al. 1992). For example, in tissue injury, the soluble syndecan-1 ectodomains are cleaved by heparanases. This results in heparin-like fragments that activate FGF.

Cell adhesion: Syndecans bind to structural extracellular matrix molecules such as collagens I, III, V, fibronectin, thrombospondin and tenascin to structurally support adhesion. Evidence for the role of syndecane in cell-cell adhesion comes from the human myeloma cell line. These myeloma cells showed a reduced ability to adhere to each other. This deficiency is attributed to the lack of syndecan 1 expression. Syndecan 4 also interacts with integrin proteins for cell-cell adhesion

Tumor suppression: Syndecanes act as tumor inhibitors by preventing cell proliferation of tumor cell lines, such as carcinoma cell lines. Furthermore, the expression of syndecan 1 plays a role in tumor progression in myeloma (David, G 1993).

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2. Bernfield M et al (1992) Biology of syndecans: a family of transmembrane heparan sulfate proteoglycans. Annu Rev Cell Biol 8: 365-393.
3. David, G (1993). Integral membrane heparan sulfate proteoglycans. FASEB J 7: 1023-1030.
4. Sungmun Choiet al (2005) "Transmembrane Domain-induced Oligomerization Is Crucial for the Functions of Syndecan-2 and Syndecan-4*". The Journal of Biological Chemistry 280: 42573-42579.
5. Zhang Y et al (2013) Targeting of heparanase-modified syndecan-1 by prosecretory mitogen lacritin requires conserved core GAGAL plus heparan and chondroitin sulfate as a novel hybrid binding site that enhances selectivity. The Journal of Biological Chemistry 288: 12090-12101
6. Chelariu-Raicu A et al (2016) Syndecan-4 expression is upregulated in endometriosis and contributes to an invasive phenotype. Fertility and Sterility 106: 378-385