SEPARATE CELL-BINDING SITES WITHIN CYTOTACTIN TENASCIN DIFFERENTIALLYPROMOTE NEURITE OUTGROWTH

Cytotactin/tenascin (CT/TN) is an extracellular matrix protein that bi nds to a variety of cell types and that influences neurite outgrowth. It has a multidomain structure with regions homologous to epidermal gr owth factor (EGF)-like repeats, fibronectin (FN) type III repeats, and the beta and gamma chains of fibrinogen (fg). The current study demon strates that a fusion protein corresponding to the sixth fibronectin t ype III repeat in CT/TN (CTfn6) supported cell attachment and promoted an increase in the number of cells with neurites in both central and peripheral neurons in tissue culture. The third fibronectin type III r epeat, CTfn3, like intact CT/TN, supported attachment of peripheral ne urons but not of central neurons and, while it caused an increase in n eurite length, it did not increase the number of cells that sprouted n eurites. When CTfn3 and CTfn6 were combined, an increase in both the n umber of cells sprouting neurites and in neurite length was observed f or peripheral neurons that resembled their response to intact CT/TN. C ell attachment to CTfn6 was inhibited in the presence of function-bloc king antibodies against pi integrins. In contrast, the interaction wit h CTfn3 was not inhibited by antibodies to pi integrins, but was inhib ited by RGD-containing peptides. The results suggest that cell binding to CT/TN involves two different sites within the molecule and occurs via different receptors which may be differentially expressed on diffe rent neuronal cell types. The location of these sites within the whole molecule in the context of other adhesive and counteradhesive domains may modulate their influence on cellular responses such as cell attac hment and neurite outgrowth.