REVIEW Syndecans as receptors and organizers of the extracellular matrix Xiaojie Xian & Sandeep Gopal & John R. Couchman Received: 20 April 2009 / Accepted: 17 June 2009 / Published online: 14 July 2009 # Springer-Verlag 2009 Abstract Syndecans are type I transmembrane proteins having a core protein modified with glycosaminoglycan chains, most commonly heparan sulphate. They are an ancient group of molecules, present in invertebrates and vertebrates. Among the plethora of molecules that can interact with heparan sulphate, the collagens and glyco- proteins of the extracellular matrix are prominent. Fre- quently, they do so in conjunction with other receptors, most notably the integrins. For this reason, they are often referred to as “co-receptors”. However, just as with integrins, syndecans can interact with actin-associated proteins and signalling molecules, such as protein kinases. Some aspects of syndecan signalling are understood but much remains to be learned. The functions of syndecans in regulating cell adhesion and extracellular matrix assembly are described here. Evidence from null mice suggests that syndecans have roles in postnatal tissue repair, inflamma- tion and tumour progression. Developmental deficits in lower vertebrates in which syndecans are eliminated are also informative and suggest that, in mammals, redundancy is a key issue. Keywords Proteoglycan . Heparan sulphate . Signalling . Extracellular matrix assembly Introduction Syndecans are type I transmembrane cell surface heparan sulphate proteoglycans (HSPGs). Four syndecan family members occur in vertebrates: syndecan-1, -2, -3 and -4. Most cell types, with the exception of erythrocytes, express at least one syndecan family member and a few may even express all four. However, syndecan-1 is expressed mostly in epithelial cells, syndecan-2 is present in cells of mesenchymal origin, syndecan-3 is primarily found in neuronal tissues but is more widely in development, whereas syndecan-4 exhibits a much broader distribution. Syndecans are now considered to have important roles during development, wound healing, inflammation and tumour progression. However, no developmental phenotype is evident in either syndecan-1 or -4 null mice, although neuronal deficits have been found in the syndecan-3 null mouse (Hienola et al. 2006). Roles in development for the syndecans are more apparent in lower vertebrates (Muñoz et al 2006; Matthews et al 2008; Kuriyama and Mayor 2009; Olivares et al. 2009). Syndecans can bind a wide array of ligands via their heparan sulphate chains and evidence is accumulating that they have roles in cell-matrix interactions and, in some cases, matrix assembly. In addition, all syndecans have been shown to interact with actin-associated proteins and, at least in the case of syndecan-4, evidence has been presented for signalling to the cytoskeleton (Couchman 2003; Morgan et al. 2007). Since a functional actin cytoskeleton is a requirement for extracellular matrix (ECM) assembly, this supports a role for the syndecans. In contrast, little evidence is available Xiaojie Xian and Sandeep Gopal contributed equally to this work. The authors are supported by the Danish National Research Foundation, the Danish Medical Research Council, Vilhelm Pedersen Fonden, Haensch Fonden, Mizutani Foundation for Glycoscience, Grosserer Ernst Fischers mindelegat and the Department of Biomedical Sciences at the University of Copenhagen. S.G. is supported by the Faculty of Health Sciences and the Molecular Mechanisms of Disease PhD programme at the University of Copenhagen. X. Xian : S. Gopal : J. R. Couchman (*) Department of Biomedical Sciences, University of Copenhagen, Biocenter, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark e-mail: john.couchman@bric.ku.dk Cell Tissue Res (2010) 339:31–46 DOI 10.1007/s00441-009-0829-3