Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology.
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.
Kupzig
Sabine
S
Department of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.
Korolchuk
Viktor
V
Rollason
Ruth
R
Sugden
Anna
A
Wilde
Andrew
A
Banting
George
G
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000954:Antigens, Surface; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D019084:Fluorescent Antibody Technique, Indirect; D058851:GPI-Linked Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D000074010:Bone Marrow Stromal Antigen 2
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C511596:Bst2 protein, rat; D000074010:Bone Marrow Stromal Antigen 2