A Transferrin-Binding Protein in Trypanosoma brucei: Does it Function in Iron Uptake?

Overath, Peter; Schell, Dietmar; Stierhof, York‐Dieter; Schwarz, Heinz; Preis, Dagmar

doi:10.1007/978-3-662-02860-5_25

Cited by 5 publications

(2 citation statements)

References 56 publications

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“…Bloodstream forms showed a strong labeling at the cell surface, the membrane lining the flagellar pocket, and components [Le., mediumderived transferrin; cf. Overath et al (1992) ] in the lumen of the flagellar pocket, which declined after 6 h. Furthermore, the membrane of intracellular vesicles close to the flagellar pocket was labeled, showing that VSG was taken up by endocytosis. However, the small size of these vesicles (100-nm diameter) did not allow us to decide if their lumen became filled with labeled material at the time (6 h, cf.…”

Section: Discussionmentioning

confidence: 98%

Proteolytic release of cell surface proteins during differentiation of Trypanosoma brucei

Ziegelbauer¹,

Stahl²,

Karas³

et al. 1993

Biochemistry

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The surface of the bloodstream forms of Trypanosoma brucei is covered by the abundant glycosylphosphatidylinositol-anchored variant surface protein (mfVSG). During differentiation of bloodstream forms to the insect-stage or procyclic forms, the mfVSG is replaced by another glycoprotein, designated procyclic acidic repetitive protein (PARP) or procyclin. Shortly after differentiation is triggered in vitro, a cell-associated fragment of mfVSG can be detected which is subsequently released into the culture medium. In the case of the mfVSG of the variant clone MITat 1.4 (470 amino acid residues), fragmentation occurs close to the COOH-terminus (Gln433 or Thr434) as shown by NH2-terminal sequencing, metabolic labeling experiments, and molecular weight determinations by laser desorption/ionization mass spectrometry. Two invariant surface glycoproteins, which are anchored in the membrane by hydrophobic sequences close to their COOH-termini, are lost from the surface with similar kinetics as mfVSG. The data suggest that trypanosomes synthesize or activate a developmentally-regulated proteinase which degrades the glycoproteins at the surface, at the membrane lining the flagellar pocket, and/or in an early endocytic compartment.

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Section: Discussionmentioning

confidence: 98%

Proteolytic release of cell surface proteins during differentiation of Trypanosoma brucei

Ziegelbauer¹,

Stahl²,

Karas³

et al. 1993

Biochemistry

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“…African trypanosomes cover their iron need by taking up host transferrin (Tf) (3)(4)(5). Uptake occurs in the flagellar pocket (3,6,7), an invagination of the plasma membrane where all endocytosis and traffic to the trypanosome surface takes place (8 -12), and is mediated by a transferrin receptor (Tf-R), a heterodimer consisting of subunits encoded by expression site-associated gene (ESAG) 6 and 7 (13)(14)(15)(16)(17), which are located in the telomeric VSG gene expression sites (for review, see Refs. 18 -21).…”

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confidence: 99%

Factors Affecting the Level and Localization of the Transferrin Receptor in Trypanosoma brucei

Mußmann

Engstler

Gerrits

et al. 2004

Journal of Biological Chemistry

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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 onetenth 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.The unicellular protozoan parasite Trypanosoma brucei can infect a broad range of mammals. It multiplies extracellularly in blood and escapes elimination by the immune system through antigenic variation of its surface coat, which consists of one major protein species, the variant surface glycoprotein (VSG), 1 attached to the plasma membrane by a glycosylphosphatidylinositol anchor (1, 2). African trypanosomes cover their iron need by taking up host transferrin (Tf) (3-5). Uptake occurs in the flagellar pocket (3, 6, 7), an invagination of the plasma membrane where all endocytosis and traffic to the trypanosome surface takes place (8 -12), and is mediated by a transferrin receptor (Tf-R), a heterodimer consisting of subunits encoded by expression site-associated gene (ESAG) 6 and 7 (13-17), which are located in the telomeric VSG gene expression sites (for review, see .The ESAG6 subunit of about 400 amino acids is attached to the plasma membrane by a glycosylphosphatidylinositol anchor; ESAG7 of about 340 amino acids remains membraneattached by holding on to ESAG6 (for review, see Ref. 22). The trypanosomal Tf-R resembles VSG dimers in apparent structure and (distantly) in sequence (23), and it is unlike other Tf-Rs in nature.

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Endocytosis in African Trypanosomes

Nolan

García‐Salcedo

Geuskens

et al.

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A Transferrin-Binding Protein in Trypanosoma brucei: Does it Function in Iron Uptake?

Cited by 5 publications

References 56 publications

Proteolytic release of cell surface proteins during differentiation of Trypanosoma brucei

Proteolytic release of cell surface proteins during differentiation of Trypanosoma brucei

Factors Affecting the Level and Localization of the Transferrin Receptor in Trypanosoma brucei

Endocytosis in African Trypanosomes

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