Thy-1, discovered almost 50 years ago, was for many years a subject of great scientific interest. The putative functions attributed to this molecule could not be confirmed due, at least in part, to a ligand that took a long time to be identified. This chapter describes the properties of Thy-1 and the regulation of its expression. Also, the interactions that have been described for Thy-1 in both cis and trans, and the signaling mechanisms reported to emanate from such interactions are discussed. The consequences of Thy-1-activated signaling pathways for different cell types and organisms are also reviewed. Since the discovery of αVβ3 integrin as a receptor for Thy-1 in astrocytes, many more functions have been attributed to Thy-1 interactions in trans toward other cell types. Recently, a ligand for neuronal Thy-1 was unveiled and shown to elicit signaling in cis. The ligand and the receptor for Thy-1 turned out to be the same molecule, αVβ3 integrin, which upon interaction with Thy-1 yields bidirectional astrocyte-to-neuron communication. Thus, Thy-1 biology is again beginning to make progress in answering main questions surrounding this enigmatic molecule. Some of these remaining questions are highlighted in this chapter.
Keywords: Cell signaling; Cellular responses; Cis–trans interactions; Ligands; Receptors; Thy-1.
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