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, located upstream of the variant surface glycoprotein gene in a polycistronic expression site form a glycosylphosphatidylinositol-anchored transferrin-binding protein (TFBP) complex. It is shown by gel filtration and membrane-binding experiments that the TFBP complex is heterodimeric and binds one molecule of transferrin with high affinity (2,300 binding sites per cell; KD = 2.1 nM for the dominant expression site from T. brucei strain 427 and KD = 131 nM for ES1.3A of the EATRO 1125 stock). The ternary transferrin-TFBP complexes with iron-loaded or iron-free ligand are stable between pH 5 and 8. Cellular transferrin uptake can be inhibited by 90% with Fab fragments from anti-TFBP antibodies. After uptake, the TFBP complex and its ligand are routed to lysosomes where transferrin is proteolytically degraded. While the degradation products are released from the cells, iron remains cell associated and the TFBP complex is probably recycled to the membrane of the flagellar pocket, the only site for exo- and endocytosis in this organism. It is concluded that the TFBP complex serves as the receptor for the uptake of transferrin in T. brucei by a mechanism distinct from that in mammalian cells.
Steverding
D
D
Max-Planck-Institut für Biologie, Abteilung Membranbiochemie, Tübingen, Federal Republic of Germany.
Stierhof
Y D
YD
Fuchs
H
H
Tauber
R
R
Overath
P
P
D000818:Animals; D002417:Cattle; D002460:Cell Line; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000737:chemistry / Q000378:metabolism*; D018411:Spodoptera; D014168:Transferrin / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000378:metabolism*
C090143:ESAG 6 protein, Trypanosoma brucei; D006023:Glycoproteins; D015800:Protozoan Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; C078011:ESAG 7 protein, Trypanosoma brucei