TRANSFERRIN-BINDING PROTEIN COMPLEX IS THE RECEPTOR FOR TRANSFERRIN UPTAKE IN TRYPANOSOMA-BRUCEI

In Trypanosoma brucei, the products of two genes, ESAG 6 and ESAG 7, l ocated upstream of the variant surface glycoprotein gene in a polycist ronic expression site form a glycosylphosphatidylinositol-anchored tra nsferrin-binding protein (TFBP) complex. It is shown by gel filtration and membrane-binding experiments that the TFBP complex is heterodimer ic and binds one molecule of transferrin with high affinity (2,300 bin ding sites per cell; K-D = 2.1 nM for the dominant expression site fro m T. brucei strain 427 and K-D = 131 nM for ES1.3A of the EATRO 1125 s tock). The ternary transferrin-TFBP complexes with iron-loaded or iron -free Ligand are stable between pH 5 and 8. Cellular transferrin uptak e can be inhibited by 90% with Fab fragments from anti-TFBP antibodies . After uptake, the TFBP complex and its ligand are routed to lysosome s where transferrin is proteolytically degraded. While the degradation products are released from the cells, iron remains cell associated an d the TFBP complex is probably recycled to the membrane of the flagell ar pocket, the only site for exo- and endocytosis in this organism. It is concluded that the TFBP complex serves as the receptor for the upt ake of transferrin in T. brucei by a mechanism distinct from that in m ammalian cells.