Tat, the transactivator protein of HIV-1, has the unusual property of being released by expressing cells and getting internalized by other neighboring cells. Here we provide genetic and biochemical evidences that cell membrane heparan sulfate (HS) proteoglycans act as receptors for extracellular Tat internalization.
Cells genetically defective in the biosynthesis of fully sulfated HS are selectively impaired in Tat internalization, but not in its extracellular release. In wild type cells, Tat uptake is competitively inhibited by soluble heparin and by treatment with glycosaminoglycan lyases specifically degrading HS chains.
Consistent
with the ubiquitous distribution of HS proteoglycans, fusion of heterologous
proteins with Tat allows their efficient intracellular delivery in different
mammalian cell types.
J. Biol. Chem.,276: 3254-3261 (2001)