title: The expression level determines the surface distribution of the transferrin receptor in Trypanosoma brucei.
abstract: The transferrin receptor (TfR) of Trypanosoma brucei is a heterodimer attached to the surface membrane by a glycosylphosphatidylinositol (GPI) anchor. The TfR is restricted to the flagellar pocket, a deep invagination of the plasma membrane. The membrane of the flagellar pocket and the rest of the cell surface are continuous, and the mechanism that selectively retains the TfR in the pocket is unknown. Here, we report that the TfR is retained in the flagellar pocket by a specific and saturable mechanism. In bloodstream-form trypanosomes transfected with the TfR genes, TfR molecules escaped flagellar pocket retention and accumulated on the entire surface, even at modest (threefold) overproduction levels. Similar surface accumulation was observed when the TfR levels were physiologically upregulated threefold when trypanosomes were starved for transferrin. These results suggest that the TfR flagellar pocket retention mechanism is easily saturated and that control of the expression level is critical to maintain the restricted surface distribution of the receptor.
authors.affiliation: Division of Molecular Biology, and Center for Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
authors.forename: Rainer
authors.initials: R
authors.lastname: Mussmann
authors.forename: Hans
authors.initials: H
authors.lastname: Janssen
authors.forename: Jero
authors.initials: J
authors.lastname: Calafat
authors.forename: Markus
authors.initials: M
authors.lastname: Engstler
authors.forename: Iris
authors.initials: I
authors.lastname: Ansorge
authors.forename: Christine
authors.initials: C
authors.lastname: Clayton
authors.forename: Piet
authors.initials: P
authors.lastname: Borst
mesh_terms: D000818:Animals; D002460:Cell Line; D005407:Flagella / Q000737:chemistry; D005786:Gene Expression Regulation / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000032:analysis; D016253:Microscopy, Immunoelectron; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D014168:Transferrin / Q000235:genetics / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000737:chemistry / Q000378:metabolism*
chemical_list: C090143:ESAG 6 protein, Trypanosoma brucei; D006023:Glycoproteins; D017261:Glycosylphosphatidylinositols; D015800:Protozoan Proteins; D014168:Transferrin; C078011:ESAG 7 protein, Trypanosoma brucei