title: CD36-related protein in Schistosoma japonicum: candidate mediator of selective cholesteryl ester uptake from high-density lipoprotein for egg maturation.
abstract: Familial cholesteryl ester transfer protein (CETP) deficiency is more common in some East Asian populations than elsewhere, suggesting the possibility of a selective advantage of this genetic defect against regional infectious diseases. Historically, infection with the Asian blood fluke Schistosoma japonicum has been endemic in these regions, including Japan. We previously reported that eggs of S. japonicum require cholesteryl ester uptake from normal high-density lipoprotein (HDL) but not from CETP-deficient HDL for their maturation to miracidia, a critical step of the hepatic pathogenesis of schistosomiasis. Herein we show that cholesteryl ester uptake is selective from HDL, and identified CD36-related protein (CD36RP) as a candidate to mediate the reaction. CD36RP was cloned from the adult and the egg developmental stages of S. japonicum, with 1880 bp encoding 506 amino acid residues exhibiting the CD36 domains and two transmembrane regions. Using antibodies against recombinant peptides representing the potential extracellular domains of CD36RP, Western blotting detected a protein with a molecular mass of 82 kDa in the particulate fraction of the adult parasite cells, which was reduced to 62 kDa after N-glycanase treatment. The extracellular domain peptide bound human HDL, as established by immunoblots following nondenaturing gel electrophoresis. Antibodies against the extracellular domain suppressed HDL cholesteryl ester uptake and maturation of the eggs in vitro. CD36RP is a candidate receptor on eggs of S. japonicum that facilitates uptake of HDL cholesteryl ester necessary for egg embryonation and maturation.
authors.affiliation: Nutritional Health Science Research Centre and Food and Nutritional Sciences, Chubu University, Kasugai 487-8501, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Okumura-Noji
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Miura
authors.forename: Rui
authors.initials: R
authors.lastname: Lu
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Asai
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ohta
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brindley
authors.forename: Shinji
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D001483:Base Sequence; D053480:Cholesterol Ester Transfer Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007564:Japan; D008052:Lipid Metabolism, Inborn Errors / Q000453:epidemiology; D008075:Lipoproteins, HDL / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010063:Ovum / Q000378:metabolism*; D011485:Protein Binding; D012549:Schistosoma japonicum / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D012554:Schistosomiasis japonica / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D015801:Helminth Proteins; D008075:Lipoproteins, HDL