Tenascin-C: Its functions as an integrin ligand

This review summarizes the experimental evidence of tenascin-C/integrin interactions, emphasizing the identification of integrin binding sites and the effects of specific interactions on cell behavior. At least four integrins appear to bind to the third fibronectin-type 3 domain of tenascin-C: alpha 9 beta 1, alpha V beta 3, alpha 8 beta 1 and alpha V beta 6. The alpha 9 beta 1 integrin recognizes a highly conserved IDG motif in this domain, while the others recognize an RGD motif. There is also significant evidence that the collagen receptor a2 beta 1 can bind to tenascin-C, but the interacting site is unknown. Tenascin-C interactions with alpha 9 beta 1 and alpha V beta 3 can promote cell proliferation and interactions with alpha V beta 3 can also inhibit apoptosis. Interactions with alpha 7 beta 1 integrin, which may bind to the alternatively spliced domain of tenascin-C, and alpha 9 beta 1 integrin are able to influence the differentiation of mesenchymal stem cells into the neuronal lineage. This illustrates the potential for using our knowledge of tenascins and their integrin receptors in stem cell-based therapies. (C) 2015 Elsevier Ltd. All rights reserved.