Receptor Tyrosine Phosphatase-δ Is a Homophilic, Neurite-Promoting Cell Adhesion Molecule for CNS Neurons

Appropriate regulation of tyrosine phosphorylation is essential for axon growth and guidance; evidence from invertebrates indicates that receptor-type tyrosine phosphatases (RPTPs) are required for correct axon growth during CNS development. One vertebrate RPTP, PTP-delta, is highly expressed in brain and has a cell adhesion molecule-like extracellular domain (ECD) comprising three immunoglobulin repeats and eight fibronectin type III repeats. Using fluorescent beads (Covaspheres) coated with the PTP-delta ECD, as well as insect cells expressing PTP-delta on their surfaces, we show that PTP-delta is a homophilic cell adhesion molecule. A variety of chick neurons adhere strongly to an Fc fusion protein containing the PTP-delta ECD. Additionally, substrate-bound PTP-delta ECD fusion protein strongly promotes neurite outgrowth from forebrain neurons; this effect is separable from its effect on adhesion. Our results indicate that PTP-delta is a neurite-promoting cell adhesion molecule for CNS neurons.