title: Apolipoprotein L-I is the trypanosome lytic factor of human serum.
abstract: Human sleeping sickness in east Africa is caused by the parasite Trypanosoma brucei rhodesiense. The basis of this pathology is the resistance of these parasites to lysis by normal human serum (NHS). Resistance to NHS is conferred by a gene that encodes a truncated form of the variant surface glycoprotein termed serum resistance associated protein (SRA). We show that SRA is a lysosomal protein, and that the amino-terminal alpha-helix of SRA is responsible for resistance to NHS. This domain interacts strongly with a carboxy-terminal alpha-helix of the human-specific serum protein apolipoprotein L-I (apoL-I). Depleting NHS of apoL-I, by incubation with SRA or anti-apoL-I, led to the complete loss of trypanolytic activity. Addition of native or recombinant apoL-I either to apoL-I-depleted NHS or to fetal calf serum induced lysis of NHS-sensitive, but not NHS-resistant, trypanosomes. Confocal microscopy demonstrated that apoL-I is taken up through the endocytic pathway into the lysosome. We propose that apoL-I is the trypanosome lytic factor of NHS, and that SRA confers resistance to lysis by interaction with apoL-I in the lysosome.
authors.affiliation: Laboratory of Molecular Parasitology, IBMM, University of Brussels, 12, rue des Profs Jeener et Brachet, B6041 Gosselies, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Vanhamme
authors.forename: Françoise
authors.initials: F
authors.lastname: Paturiaux-Hanocq
authors.forename: Philippe
authors.initials: P
authors.lastname: Poelvoorde
authors.forename: Derek P
authors.initials: DP
authors.lastname: Nolan
authors.forename: Laurence
authors.initials: L
authors.lastname: Lins
authors.forename: Jan
authors.initials: J
authors.lastname: Van Den Abbeele
authors.forename: Annette
authors.initials: A
authors.lastname: Pays
authors.forename: Patricia
authors.initials: P
authors.lastname: Tebabi
authors.forename: Huang
authors.initials: H
authors.lastname: Van Xong
authors.forename: Alain
authors.initials: A
authors.lastname: Jacquet
authors.forename: Nicole
authors.initials: N
authors.lastname: Moguilevsky
authors.forename: Marc
authors.initials: M
authors.lastname: Dieu
authors.forename: John P
authors.initials: JP
authors.lastname: Kane
authors.forename: Patrick
authors.initials: P
authors.lastname: De Baetselier
authors.forename: Robert
authors.initials: R
authors.lastname: Brasseur
authors.forename: Etienne
authors.initials: E
authors.lastname: Pays
mesh_terms: D000818:Animals; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D004198:Disease Susceptibility; D004705:Endocytosis; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D015800:Protozoan Proteins; D016833:Trypanosoma brucei rhodesiense / Q000378:metabolism* / Q000472:pathogenicity
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; C403774:serum resistance associated protein, Trypanosoma brucei