title: The tegument of the human parasitic worm Schistosoma mansoni as an excretory organ: the surface aquaporin SmAQP is a lactate transporter.
abstract: Adult schistosomes are intravascular parasites that metabolize imported glucose largely via glycolysis. How the parasites get rid of the large amounts of lactic acid this generates is unknown at the molecular level. Here, we report that worms whose aquaporin gene (SmAQP) has been suppressed using RNAi fail to rapidly acidify their culture medium and excrete less lactate compared to controls. Functional expression of SmAQP in Xenopus oocytes demonstrates that this protein can transport lactate following Michaelis-Menten kinetics with low apparent affinity (Km = 41+/-5. 8 mM) and with a low energy of activation (E(a) = 7.18+/-0.7 kcal/mol). Phloretin, a known inhibitor of lactate release from schistosomes, also inhibits lactate movement in SmAQP-expressing oocytes. In keeping with the substrate promiscuity of other aquaporins, SmAQP is shown here to be also capable of transporting water, mannitol, fructose and alanine but not glucose. Using immunofluorescent and immuno-EM, we confirm that SmAQP is localized in the tegument of adult worms. These findings extend the proposed functions of the schistosome tegument beyond its known capacity as an organ of nutrient uptake to include a role in metabolic waste excretion.
authors.affiliation: Molecular Helminthology Laboratory, Division of Infectious Diseases, Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, Grafton, Massachusetts, United States of America.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Faghiri
authors.forename: Simone M R
authors.initials: SM
authors.lastname: Camargo
authors.forename: Katja
authors.initials: K
authors.lastname: Huggel
authors.forename: Ian C
authors.initials: IC
authors.lastname: Forster
authors.forename: David
authors.initials: D
authors.lastname: Ndegwa
authors.forename: François
authors.initials: F
authors.lastname: Verrey
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Skelly
mesh_terms: D000818:Animals; D020346:Aquaporins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003470:Culture Media; D006376:Helminths / Q000033:anatomy & histology* / Q000378:metabolism*; D007150:Immunohistochemistry; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D009995:Osmosis; D012550:Schistosoma mansoni / Q000033:anatomy & histology* / Q000166:cytology / Q000378:metabolism*; D014981:Xenopus
chemical_list: D020346:Aquaporins; D003470:Culture Media; D027501:Monocarboxylic Acid Transporters
references.citation: Exp Parasitol. 2006 Nov;114(3):180-8
references.pmid: 16682030
references.citation: FASEB J. 2009 Aug;23(8):2780-9
references.pmid: 19364765
references.citation: Mol Cell Proteomics. 2006 Feb;5(2):347-56
references.pmid: 16269422
references.citation: Parasitology. 1991 Apr;102 Pt 2:259-65
references.pmid: 1906594
references.citation: Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3642-6
references.pmid: 8622989
references.citation: Parasitology. 2001 Sep;123(Pt 3):277-84
references.pmid: 11578091
references.citation: Parasitology. 2001 Jan;122 Pt 1:67-73
references.pmid: 11197766
references.citation: J Biol Chem. 1998 Sep 18;273(38):24737-43
references.pmid: 9733774
references.citation: Xenobiotica. 2008 Jul;38(7-8):1072-106
references.pmid: 18668440
references.citation: J Gen Physiol. 1950 May 20;33(5):475-95
references.pmid: 15422103
references.citation: Science. 1992 Apr 17;256(5055):385-7
references.pmid: 1373524
references.citation: Q Rev Biophys. 2006 Nov;39(4):361-96
references.pmid: 17156589
references.citation: J Biol Chem. 1996 Oct 11;271(41):25079-82
references.pmid: 8810261
references.citation: Mol Biochem Parasitol. 2005 Oct;143(2):209-15
references.pmid: 16076506
references.citation: Parasite Immunol. 2003 Aug-Sep;25(8-9):429-37
references.pmid: 14651590
references.citation: Biochem J. 2000 Aug 15;350 Pt 1:219-27
references.pmid: 10926847
references.citation: Mol Biochem Parasitol. 1990 Mar;39(2):195-201
references.pmid: 2108329
references.citation: Exp Parasitol. 1989 Feb;68(2):235-7
references.pmid: 2494055
references.citation: J Membr Biol. 2007 Feb;215(2-3):81-92
references.pmid: 17443384
references.citation: Lancet. 2006 Sep 23;368(9541):1106-18
references.pmid: 16997665
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: J Biol Chem. 1990 Sep 15;265(26):15375-8
references.pmid: 2394728
references.citation: Proteomics. 2006 Mar;6(5):1471-82
references.pmid: 16447162
references.citation: Drug Metab Pharmacokinet. 2008;23(4):279-84
references.pmid: 18762715
references.citation: Nature. 1998 Sep 17;395(6699):288-91
references.pmid: 9751058
references.citation: J Biol Chem. 1994 Feb 11;269(6):4247-53
references.pmid: 8307988
references.citation: Adv Parasitol. 2006;63:185-284
references.pmid: 17134654
references.citation: Am J Physiol. 1999 Nov;277(5):F685-96
references.pmid: 10564231
references.citation: Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7212-6
references.pmid: 7543677
references.citation: Exp Parasitol. 1982 Dec;54(3):379-90
references.pmid: 7151946
references.citation: Biol Cell. 2008 Jun;100(6):355-63
references.pmid: 18167118
references.citation: Int J Parasitol. 2000 Apr 24;30(5):625-31
references.pmid: 10779576
references.citation: Mol Biochem Parasitol. 1984 Sep;13(1):39-51
references.pmid: 6513987
references.citation: J Biol Chem. 2007 Jul 27;282(30):21767-75
references.pmid: 17545149
references.citation: Histol Histopathol. 2009 Feb;24(2):243-64
references.pmid: 19085840
references.citation: Parasitol Today. 1998 Oct;14(10):402-6
references.pmid: 17040830
references.citation: J Biol Chem. 1997 Aug 15;272(33):20782-6
references.pmid: 9252401