Document 0296
 DOCN  M9460296
 TI    Targeting of liposomes to cells expressing CD4 using
       glycosylphosphatidylinositol-anchored gp120. Influence of liposome
       composition on intracellular trafficking.
 DT    9404
 AU    Schreier H; Moran P; Caras IW; Department of Neurobiology, Genentech,
       Inc., South San Francisco,; California 94080.
 SO    J Biol Chem. 1994 Mar 25;269(12):9090-8. Unique Identifier : AIDSLINE
       MED/94179327
 AB    To test the concept that glycosylphosphatidylinositol (GPI)-anchored
       proteins might be useful as targeting molecules for liposomes, we
       engineered a GPI-anchored form of gp120 from human immunodeficiency
       virus type 1 (termed gp120DAF) using the GPI signal of
       decay-accelerating factor (DAF). We show that (i) purified gp120DAF
       spontaneously inserts into liposome membranes via the GPI anchor; (ii)
       liposomes bearing gp120DAF bind specifically to cells expressing CD4,
       the cellular receptor for gp120; and (iii) the receptor-bound liposomes
       are internalized and recycle in Chinese hamster ovary cells. To test
       whether the lipid composition of the liposome affects any of these
       processes, we compared small unilamellar liposomes containing only
       phosphatidylcholine and cholesterol in a 7:1 molar ratio with artificial
       viral envelopes that mimic the lipid composition of human
       immunodeficiency virus type 1. We show that when tagged with gp120DAF,
       both liposome preparations bind specifically to cells expressing CD4,
       and both are endocytosed. However, artificial viral envelope liposomes
       are transported to late endosomes or lysosomes in the cell interior,
       whereas phosphatidylcholine:cholesterol liposomes are confined to a
       population of vesicles that remain close to the plasma membrane. Since
       the binding and internalization of both liposome preparations are
       mediated by the same receptor, we conclude that the lipid composition of
       the liposome profoundly influences the subsequent intracellular
       trafficking of the liposome-receptor complex.
 DE    Animal  Antigens, CD4/*METABOLISM  CHO Cells  Endocytosis
       *Glycosylphosphatidylinositols  Hamsters  HIV Envelope Protein
       gp120/*CHEMISTRY  Liposomes/*CHEMISTRY  Recombinant Proteins
       Transfection  T4 Lymphocytes/*METABOLISM  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).