Apolipoprotein L-I is the trypanosome lytic factor of human serum.
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.
Vanhamme
Luc
L
Laboratory of Molecular Parasitology, IBMM, University of Brussels, 12, rue des Profs Jeener et Brachet, B6041 Gosselies, Belgium.
Paturiaux-Hanocq
Françoise
F
Poelvoorde
Philippe
P
Nolan
Derek P
DP
Lins
Laurence
L
Van Den Abbeele
Jan
J
Pays
Annette
A
Tebabi
Patricia
P
Van Xong
Huang
H
Jacquet
Alain
A
Moguilevsky
Nicole
N
Dieu
Marc
M
Kane
John P
JP
De Baetselier
Patrick
P
Brasseur
Robert
R
Pays
Etienne
E
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
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