title: Factors affecting the level and localization of the transferrin receptor in Trypanosoma brucei.
abstract: Transfer of bloodstream-form Trypanosoma brucei variant 221a from calf serum to dog serum-based medium induces acute iron starvation, as the transferrin receptor (Tf-R) of variant 221a binds dog Tf poorly. We show here that transfer to dog serum induces a 3-5-fold increase in Tf-R mRNA and protein within one doubling time (8 h). Because iron stores are still high 8 h after transfer, we infer that the signal for Tf-R overproduction is the decreased availability of cytosolic iron when cellular iron import drops. Up to 30% of the extra Tf-R spills out of the flagellar pocket onto the pellicular surface. Because the 5-fold increase in Tf-R is accompanied by a 5-fold increase in bovine Tf uptake, the up-regulation of Tf-R levels in response to Tf starvation helps the trypanosome to compete for limiting amounts of Tf. We noted that Tf-R levels also vary in calf serum medium. Cells in dense cultures contain up to 5-fold more Tf-R mRNA and protein than in dilute cultures. Only one-tenth of the extra Tf-R reaches the pellicular surface. The increase cannot be explained by a lack of Tf or to cell density sensing but is due to pericellular hypoxia. Our results show that bloodstream-form trypanosomes can regulate the expression of the two Tf-R subunit genes and the localization of their gene products in a flexible manner. This flexibility is made possible by the promoter-proximal position of the two genes in the variant surface glycoprotein expression site.
authors.affiliation: The Netherlands Cancer Institute, Division of Molecular Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Rainer
authors.initials: R
authors.lastname: Mussmann
authors.forename: Markus
authors.initials: M
authors.lastname: Engstler
authors.forename: Herlinde
authors.initials: H
authors.lastname: Gerrits
authors.forename: Rudo
authors.initials: R
authors.lastname: Kieft
authors.forename: Cristiane Bentin
authors.initials: CB
authors.lastname: Toaldo
authors.forename: Jos
authors.initials: J
authors.lastname: Onderwater
authors.forename: Henk
authors.initials: H
authors.lastname: Koerten
authors.forename: Henri G A M
authors.initials: HG
authors.lastname: van Luenen
authors.forename: Piet
authors.initials: P
authors.lastname: Borst
mesh_terms: D000818:Animals; D001665:Binding Sites; D015152:Blotting, Northern; D002417:Cattle; D003470:Culture Media / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004577:Electron Probe Microanalysis; D004705:Endocytosis; D005407:Flagella / Q000378:metabolism; D006031:Glycosylation; D000860:Hypoxia; D007501:Iron / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011990:Receptors, Transferrin / Q000096:biosynthesis* / Q000378:metabolism; D013997:Time Factors; D014346:Trypanosoma brucei brucei / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D003470:Culture Media; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D007501:Iron