Identification of a novel contactin-associated transmembrane receptor with multiple domains implicated in protein-protein interactions

Abstract

Receptor protein tyrosine phosphatase β (RPTPβ) expressed on the surface of glial cells binds to the glycosylphosphatidylinositol (GPI)‐anchored recognition molecule contactin on neuronal cells leading to neurite outgrowth. We describe the cloning of a novel contactin‐associated transmembrane receptor (p190/Caspr) containing a mosaic of domains implicated in protein–protein interactions. The extracellular domain of Caspr contains a neurophilin/coagulation factor homology domain, a region related to fibrinogen β/γ, epidermal growth factor‐like repeats, neurexin motifs as well as unique PGY repeats found in a molluscan adhesive protein. The cytoplasmic domain of Caspr contains a proline‐rich sequence capable of binding to a subclass of SH3 domains of signaling molecules. Caspr and contactin exist as a complex in rat brain and are bound to each other by means of lateral ( cis ) interactions in the plasma membrane. We propose that Caspr may function as a signaling component of contactin, enabling recruitment and activation of intracellular signaling pathways in neurons. The binding of RPTPβ to the contactin–Caspr complex could provide a mechanism for cell–cell communication between glial cells and neurons during development.