A NOVEL HETERODIMERIC TRANSFERRIN RECEPTOR ENCODED BY A PAIR OF VSG EXPRESSION SITE-ASSOCIATED GENES IN TRYPANOSOMA-BRUCEI

In T. brucei, a transferrin-binding protein has been found to share se quence homology with pESAG-7 and -6, the products of two related genes present in the VSG gene polycistronic transcription unit. When expres sed in Xenopus oocytes, they appear as N-glycosylated proteins secrete d in the medium (pESAG-7) and GPI anchored to the membrane (pESAG-6). These proteins are able to homo- or heterodimerize, probably through a ssociation in the same orientation. Only heterodimers can bind Tf, pos sibly two molecules per dimer. A comparison of Tf binding to pESAG-7/6 -expressing oocytes and trypanosomes suggests that pESAG-7/6 is the Tf receptor of the parasite. In trypanosomes, the majority of pESAG-7/6 is released from the membrane and associates, together with Tf, with a glycosylated matrix present in the lumen of the flagellar pocket. Bot h pESAG-7/6 and Tf are internalized via coated pits and vesicles. Thes e observations suggest a novel mode of Tf binding and uptake in trypan osomes.