The thrombospondin type 1 repeat (TSR) superfamily: diverse proteins with related roles in neuronal development

The thrombospondins are a family of proteins found widely in the embryonic extracellular matrix. Like most matrix proteins, thrombospondins are modular and contain a series of repeated domains arrayed between globular amino and carboxyl terminal domains. In recent years, other proteins that share thrombospondin type 1 repeats, or TSRs, have been identified. These include the F-spondin gene family, the members of the semaphorin 5 family, UNC-5, SCO-spondin, and others. Most of these are expressed in the developing nervous system, and many have expression patterns and in vitro properties that suggest potential roles in the guidance of cell and growth cone migration. Both cell- and matrix-binding motifs have been identified in the TSRs of thrombospondin-1, so it has been hypothesized that the properties of these diverse proteins may also depend on the presence of these repeats. Here, we review the cell biology of the TSR module, the extensive literature regarding the distribution and functions of thrombospondins and other TSR superfamily proteins, and evaluate their possible roles during the development of the nervous system.