The axonal glycoprotein TAG-1 is an immunoglobulin superfamily member with neurite outgrowth-promoting activity

Pathfinding of axons in the developing nervous system is thought to be mediated by glycoproteins expressed on the surface of embryonic axons and growth cones. One molecule suggested to play a role in axonal growth is TAG-1, a 135 kd glycoprotein expressed transiently on the surface of subsets of neurons in the developing mammalian nervous system. We isolated a full-length cDNA clone encoding rat TAG-1. TAG-1 has six immunoglobulin-like domains and four fibronectin type III-like repeats and is structurally similar to other immunoglobulin-like proteins expressed on developing axons. Neurons maintained in vitro on a substrate of TAG-1 extend long neurites, suggesting that this protein plays a role in the initial growth and guidance of axons in vivo. TAG-1 is anchored to the neuronal membrane via a glycosyl phosphatidylinositol linkage and is also released from neurons, suggesting that TAG-1 also functions as a substrate adhesion molecule when released into the extracellular environment.