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.

Unphosphorylated STAT1 prolongs the expression of interferon-induced immune regulatory genes

“…From results presented here, it is reasonable to propose that up-regulated STAT1 may enhance IFI27 and OAS1 expression in breast tumors. The function of BST2 also remains unknown but may be important in sorting membrane and secreted proteins in the Golgi apparatus, localized on both cell surface and intracellular compartments (23). The expression of BST2 was predominantly specific for type I IFN-producing cells in the naïve mouse and was up-regulated in most cell types after stimulation with type I IFNs or IFN-␥ (24).…”

Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion

“…Bst-2 is a 30-to 36-kDa type II transmembrane protein consisting of 180 aa (27). The protein has an unusual topology in that it has both an N-terminal transmembrane domain and a C-terminal glycosylphosphatidylinositol (GPI) anchor (28). Bst-2 associates with lipid rafts at the cell surface and was identified on internal membranes, presumably the trans-Golgi network (28).…”

The role of BST‐2/Tetherin in host protection and disease manifestation

“…1). Removal of the anchor does not affect association of BST‐2 with the cell membrane; however, lipid raft localization of BST‐2 is lost 9.…”

“…Furthermore, BST‐2 ectodomain is post‐translationally modified by N‐linked glycosylation of two asparagine residues at positions 65 and 92 9, 11, 21. Although the function of BST‐2 glycosylation for inhibition of virus release is unclear 11, 22, this post‐translational modification is important for proper folding and trafficking of BST‐2 through the endoplasmic reticulum (ER) and the Golgi 23.…”

“…Although the function of BST‐2 glycosylation for inhibition of virus release is unclear 11, 22, this post‐translational modification is important for proper folding and trafficking of BST‐2 through the endoplasmic reticulum (ER) and the Golgi 23. BST‐2 molecule associates with lipid rafts 1, 9, 13, 24, 25, 26 through the GPI anchor 9 (Fig. 1).…”