Bst‐2/HM1.24 Is a Raft‐Associated Apical Membrane Protein with an Unusual Topology

Abstract

An expression screen of a rat cDNA library for sequences encoding Golgi‐localized integral membrane proteins identified a protein with an apparent novel topology, i.e. with both an N‐terminal transmembrane domain and a C‐terminal glycosyl‐phosphatidylinositol (GPI) anchor. Our data are consistent with this. Thus, the protein would have a topology that, in mammalian cells, is shared only by a minor, but pathologically important, topological isoform of the prion protein (PrP). The human orthologue of this protein has been described previously (BST‐2 or HM1.24 antigen) as a cell surface molecule that appears to be involved in early pre‐B‐cell development and which is present at elevated levels at the surface of myeloma cells. We show that rat BST‐2/HM1.24 has both a cell surface and an intracellular (juxtanuclear) location and is efficiently internalized from the cell surface. We also show that the cell surface pool of BST‐2/HM1.24 is predominantly present in the apical plasma membrane of polarized cells. The fact that rat BST‐2/HM1.24 apparently possesses a GPI anchor led us to speculate that it might exist in cholesterol‐rich lipid microdomains (lipid rafts) at the plasma membrane. Data from several experiments are consistent with this localization. We present a model in which BST‐2/HM1.24 serves to link adjacent lipid rafts within the plasma membrane.