TAG-1 CAN MEDIATE HEMOPHILIC BINDING, BUT NEURITE OUTGROWTH ON TAG-1 REQUIRES AN L1-LIKE MOLECULE AND BETA-1 INTEGRINS

Subsets of axons in the embryonic nervous system transiently express t he glycoprotein TAG-1, a member of the subfamily of immunoglobulin (Ig )-like proteins that contain both C2 class Ig and fibronectin type III domains. TAG-1 is attached to the cell surface by a glycosylphosphati dylinositol linkage and is secreted by neurons. In vitro studies have shown that substrate-bound TAG-1 promotes neurite outgrowth. We have e xamined the nature of axonal receptors that mediate the neurite-outgro wth promoting properties of TAG-1. Although TAG-1 can mediate hemophil ic binding, neurite outgrowth on a substrate of TAG-1 does not depend on the presence of TAG-1 on the axonal surface. Instead, neurite outgr owth on TAG-1 is inhibited by polyclonal antibodies directed against L 1 and, independently, by polyclonal and monoclonal antibodies against beta 1-containing integrins. These results provide evidence that TAG-1 can interact with cell surfaces in both a hemophilic and heterophilic manner and suggest that neurite extension on TAG-1 requires the funct ion of both integrins and an L1-like molecule.