THE PERPLEXING MULTIFUNCTIONALITY OF JANUSIN, A TENASCIN-RELATED MOLECULE

The extracellular matrix glycoprotein janusin, closely related to tena scin in its repeated motifs of epidermal growth factor, fibronectin ty pe III, and fibrinogen-like domains, displays in vitro a broad spectru m of functional diversity. Synthesized by oligodendrocytes and subpopu lations of neurons at late developmental stages in the rodent central nervous system, it can be adhesive or antiadhesive, depending on the n eural cell type that interacts with it. It promotes neurite outgrowth of some neural cell types, when offered as a uniform culture substrate , but inhibits neurite outgrowth of other neuronal populations. When o ffered as a sharp substrate boundary in congruence with a permissive s ubstrate, it acts as a barrier for neurite outgrowth. Like tenascin, i t can modify the adhesive substrate properties of another extracellula r matrix glycoprotein, fibronectin, whereby the smaller, 160 kD compon ent of janusin exerts its effects by interaction with fibronectin and the 180 kD janusin component functionally modifies the fibronectin rec eptor via a disialoganglioside receptor. In neurons, the antiadhesive and neurite outgrowth inhibiting signal is mediated by the F3/11 immun oglobulin superfamily recognition molecule. In oligodendrocytes, yet a nother receptor for janusin mediates adhesion and process formation. A prerequisite for any intracellular response to occur is a transient l ock-and-key recognition manifesting itself in short-term binding betwe en the interacting partners. As for tenascin, the different functions exerted by janusin are likely to be encoded in the different domains o f the janusin molecule, which can act on different receptors, whereby the receiving cell is able to interpret the cell surface trigger in di fferent ways, depending on the particular cell type involved. These ob servations suggest that the multiplicity of janusin's functions not on ly lies in the multimodular structure of the molecule, but that the ty pe of receptor and interplay between receptors of the receiving cell m odulate the cellular response, depending on the makeup of its intracel lular second messenger systems and their interactions with the cytoske leton.