Cellular and molecular remodeling of the endocytic pathway during differentiation of Trypanosoma brucei bloodstream forms.
During the course of mammalian infection, African trypanosomes undergo extensive cellular differentiation, as actively dividing long slender (SL) forms progressively transform into intermediate (I) forms and finally quiescent G(1)/G(0)-locked short stumpy (ST) forms. ST forms maintain adaptations compatible with their survival in the mammalian bloodstream, such as high endocytic activity, but they already show preadaptations to the insect midgut conditions. The nutritional requirements of ST forms must differ from those of SL forms because the ST forms stop multiplying. We report that the uptake of several ligands was reduced in ST forms compared with that in SL forms. In particular, the haptoglobin-hemoglobin (Hp-Hb) complex was no longer taken up due to dramatic downregulation of its cognate receptor, TbHpHbR. As this receptor also allows uptake of trypanolytic particles from human serum, ST forms were resistant to trypanolysis by human serum lipoproteins. These observations allowed both flow cytometry analysis of SL-to-ST differentiation and the generation of homogeneous ST populations after positive selection upon exposure to trypanolytic particles. In addition, we observed that in ST forms the lysosome relocates anterior to the nucleus. Altogether, we identified novel morphological and molecular features that characterize SL-to-ST differentiation.
Vanhollebeke
Benoit
B
Laboratory of Molecular Parasitology, Institute of Molecular Biology and Medicine, Université Libre de Bruxelles, 12 rue des Professeurs Jeener et Brachet, B-6041 Gosselies, Belgium.
Uzureau
Pierrick
P
Monteyne
Daniel
D
Pérez-Morga
David
D
Pays
Etienne
E
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D003080:Cold Temperature; D015536:Down-Regulation / Q000235:genetics; D004705:Endocytosis; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008018:Life Cycle Stages; D008024:Ligands; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000166:cytology* / Q000235:genetics / Q000254:growth & development* / Q000648:ultrastructure
D008024:Ligands; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; C434063:TLF1 protein, human; C027079:hemoglobin-haptoglobin receptor