Blue bars: extracellular matrix molecules, including fibronectin. Pink: integrin molecules. Yellow: TG2 protein domains, note that C terminal is simplified as in reality it consists of 2 domains.

Figure 3: This is a schematic of the trangslutaminase (TG)-2 matrix interactions relevant in retinal pigment epithelial cell adhesion. First, TG2 can interact with fibronectin independently of integrin (A). Second, inhibition of TG2-fibronectin interaction involves the N terminal sandwich region of TG2 (B) rather than the transamidase (C) and GTP/GDP related activities (D) subserved by other parts of TG2. However crosslinking activity of matrix molecules by TG2 (C) is relevant in scar formation and diseases like PVR. Crosslinking activity of TG2, via the recruitment of elastase inhibitors such as elafins and cystatins, can stabilize the extracellular matrix. Lastly, TG2 can interact with fibronectin domain through integrin (E) but also independently of crosslinking and G protein function. This association occurs at focal adhesion complexes to mediate integrin signaling, again independently of its transamidase. In order to inhibit proliferative vitreoretinopathy using a TG2 based intervention, it may be necessary to target these different interfaces or interactions.