Functionally different GPI proteins are organized in different domains on the neuronal surface

We have investigated the organization, on the plasma membrane and in deterg ent-insoluble membrane vesicles, of two neuronal glycosylphosphatidylinosit ol-anchored (GPI) proteins: Thy-1, a negative regulator of transmembrane si gnalling; and prion protein, whose rapid endocytosis and Cu2+ binding sugge st that it functions in metal ion uptake. Prion protein occurred on the neu ronal surface at high density in domains, located primarily at the cell bod y, which were relatively soluble in detergent. Thy-1, although much more ab undantly expressed on neurons, occurred at lower density over much of the s urface of neurites land in lower abundance at the cell body) in domains tha t were highly resistant to detergent solubilization, Detergent-insoluble me mbrane vesicles contained Thy-1 at a density similar to that on the neurona l surface. Vesicles containing each protein could be separated by immunoaff inity isolation; lectin binding showed that they were enriched in different glycoproteins. Our results demonstrate a structural diversity of the domai ns occupied by functionally different GPI proteins.