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19. Fell-Muir Lecture: Syndecans: from peripheral coreceptors to mainstream regulators of cell behaviour.

Author

Couchman JR, Gopal S, Lim HC, Nørgaard S, and Multhaupt HA

Subjects
Animals, Genotype, Humans, Inflammation metabolism, Ligands, Mice, Knockout, Neoplasms metabolism, Phenotype, Protein Conformation, Receptors, Cell Surface chemistry, Receptors, Cell Surface deficiency, Receptors, Cell Surface genetics, Structure-Activity Relationship, Syndecans chemistry, Syndecans deficiency, Syndecans genetics, Receptors, Cell Surface metabolism, Signal Transduction, Syndecans metabolism
Abstract

In the 25 years, as the first of the syndecan family was cloned, interest in these transmembrane proteoglycans has steadily increased. While four distinct members are present in mammals, one is present in invertebrates, including C. elegans that is such a powerful genetic model. The syndecans, therefore, have a long evolutionary history, indicative of important roles. However, these roles have been elusive. The knockout in the worm has a developmental neuronal phenotype, while knockouts of the syndecans in the mouse are mild and mostly limited to post-natal rather than developmental effects. Moreover, their association with high-affinity receptors, such as integrins, growth factor receptors, frizzled and slit/robo, have led to the notion that syndecans are coreceptors, with minor roles. Given that their heparan sulphate chains can gather many different protein ligands, this gave credence to views that the importance of syndecans lay with their ability to concentrate ligands and that only the extracellular polysaccharide was of significance. Syndecans are increasingly identified with roles in the pathogenesis of many diseases, including tumour progression, vascular disease, arthritis and inflammation. This has provided impetus to understanding syndecan roles in more detail. It emerges that while the cytoplasmic domains of syndecans are small, they have clear interactive capabilities, most notably with the actin cytoskeleton. Moreover, through the binding and activation of signalling molecules, it is likely that syndecans are important receptors in their own right. Here, an overview of syndecan structure and function is provided, with some prospects for the future., (© 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.)

Published
2015
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