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

Traffic. 2003 Oct;4(10):694-709. doi: 10.1034/j.1600-0854.2003.00129.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antigens, Surface
  • COS Cells
  • Cell Line
  • Chlorocebus aethiops
  • Conserved Sequence
  • Fluorescent Antibody Technique, Indirect
  • GPI-Linked Proteins
  • Male
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism
  • Membrane Microdomains / metabolism
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Models, Biological
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal
  • Antigens, Surface
  • Bst2 protein, rat
  • GPI-Linked Proteins
  • Membrane Glycoproteins
  • Membrane Proteins