CLONING OF NEUROTRIMIN DEFINES A NEW SUBFAMILY OF DIFFERENTIALLY EXPRESSED NEURAL CELL-ADHESION MOLECULES

Previous studies in the laboratory indicated that glycosylphosphatidyl inositol (GPI)-anchored proteins may generate diversity of the cell su rface of different neuronal populations (Rosen et al., 1992). In this study, we have extended these findings and surveyed the expression of GPI-anchored proteins in the developing rat CNS. In addition to severa l well characterized GPI-anchored cell adhesion molecules (CAMs), we d etected an unidentified broad band of 65 kDa that is the earliest and most abundantly expressed GPI-anchored species in the rat CNS. Purific ation of this protein band revealed that it is comprised of several re lated proteins that define a novel subfamily of immunoglobulinlike (Ig ) CAMs. One of these proteins is the opiate binding-cell adhesion mole cule (OBCAM), We have isolated a cDNA encoding a second member of this family, that we have termed neurotrimin, and present evidence for the existence of additional family members. Like OBCAM, with which it sha res extensive sequence identity, neurotrimin contains three immunoglob ulin-like domains. Both proteins are encoded by distinct genes that ma y be clustered on the proximal end of mouse chromosome 9. Characteriza tion of the expression of neurotrimin and OBCAM in the developing CNS by in situ hybridization reveals that these proteins are differentiall y expressed during development. Neurotrimin is expressed at high level s in several developing projection systems: in neurons of the thalamus , subplate, and lower cortical laminae in the forebrain and in the pon tine nucleus, cerebellar granule cells, and Purkinje cells in the hind brain, Neurotrimin is also expressed at high levels in the olfactory b ulb, neural retina, dorsal root ganglia, spinal cord, and in a graded distribution in the basal ganglia and hippocampus, OBCAM has a much mo re restricted distribution, being expressed at high levels principally in the cortical plate and hippocampus. These results suggest that the se proteins, together with other members of this family, provide diver sity to the surfaces of different neuronal populations that could be i mportant in the specification of neuronal connectivity.