THE CARBONIC-ANHYDRASE DOMAIN OF RECEPTOR TYROSINE PHOSPHATASE-BETA IS A FUNCTIONAL LIGAND FOR THE AXONAL CELL RECOGNITION MOLECULE CONTACTIN

Receptor-type protein tyrosine phosphatase beta (RPTP beta) is express ed in the developing nervous system and contains a carbonic anhydrase (CAH) domain as well as a fibronectin type III repeat in its extracell ular domain. Fusion proteins containing these domains were used to sea rch for ligands of RPTP beta. The CAH domain bound specifically to a 1 40 kDa protein expressed on the surface of neuronal cells. Expression cloning in COS7 cells revealed that this protein is contactin, a GPI m embrane-anchored neuronal cell recognition molecule. The CAH domain of RPTP beta induced cell adhesion and neurite growth of primary tectal neurons, and differentiation of neuroblastoma cells. These responses w ere blocked by antibodies against contactin, demonstrating that contac tin is a neuronal receptor for RPTP beta. These experiments show that an individual domain of RPTP beta acts as a functional ligand for the neuronal receptor contactin. The Interaction between contactin and RPT P beta may generate unidirectional or bidirectional signals during neu ral development.