Factors affecting the level and localization of the transferrin receptor in Trypanosoma brucei.
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.
Mussmann
Rainer
R
The Netherlands Cancer Institute, Division of Molecular Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Engstler
Markus
M
Gerrits
Herlinde
H
Kieft
Rudo
R
Toaldo
Cristiane Bentin
CB
Onderwater
Jos
J
Koerten
Henk
H
van Luenen
Henri G A M
HG
Borst
Piet
P
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
D003470:Culture Media; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D007501:Iron