Syndecan-4 regulates cell-surface trafficking and biological activity of transglutaminase-2

Transglutaminase-2 (TG2) is a Ca2+-dependent crosslinking enzyme involved in the post-translational modification of proteins via the formation of Nε(γ-glutamyl)lysine isodipeptides. TG2 is externalised in the extracellular matrix (ECM) through an unconventional and not fully understood pathway. Under normal conditions, TG2 modulates cell adhesion, proliferation and tissue repair. Under continuous cell insult higher expression and elevated extracellular trafficking of TG2 contribute to the pathogenesis of tissue scarring. TG2 is known to have affinity for heparin, and in a previous study cell-surface heparan sulphate (HS) has been implicated in extracellular TG2 mediated RGD-independent cell adhesion, a non-enzymatic process independent from the α5β1 integrin-binding to the RGD domain on FN (Verderio et al., 2003). Hence HS proteoglycan (HSPG) could act as cell surface co-receptor for FNbound TG2 or contribute to the regulation of extracellular TG2 activity in cell adhesion and tissue repair