syndecans

Syndecans are a family of transmembrane heparan sulfate proteoglycans that decorate the cell surface and participate in a range of cell–matrix and cell–growth factor interactions. Each member consists of a core protein anchored in the plasma membrane and carrying glycosaminoglycan chains, predominantly heparan sulfate, with occasional chondroitin sulfate attachments. In humans there are four syndecans: syndecan-1 (CD138), syndecan-2, syndecan-3, and syndecan-4. They are variably expressed across tissues, contributing to context-specific signaling.

Syndecans function as co-receptors for numerous growth factors, morphogens, and extracellular matrix components. The heparan sulfate chains bind factors such as fibroblast growth factors, vascular endothelial growth factor, and hepatocyte growth factor, thereby modulating receptor activation. They also mediate adhesion to extracellular matrix proteins like fibronectin, collagen, and laminin, influencing cell migration, proliferation, and differentiation. The cytoplasmic tails of syndecans interact with intracellular partners, including cytoskeletal adapters and PDZ-domain proteins, linking extracellular cues to signaling pathways.

A notable feature is regulated shedding: proteolytic cleavage releases the ectodomain into the surrounding milieu, where soluble syndecans can shape signaling and inflammation. Syndecans show tissue-specific expression patterns—syndecan-1 is common in epithelial and plasma cells, syndecan-2 in fibroblasts and endothelium, syndecan-3 in the nervous system, and syndecan-4 broadly in mesenchymal tissues.

In development and disease, syndecans influence processes such as wound healing and angiogenesis, and dysregulation has been linked to cancer progression and inflammatory conditions. Research uses genetic models and biochemical approaches to elucidate their roles and potential as therapeutic targets or biomarkers.