title: Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites.
abstract: Apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. The identities of the transporters that mediate amino acid uptake into apicomplexans are unknown. Here we demonstrate that members of an apicomplexan-specific protein family-the Novel Putative Transporters (NPTs)-play key roles in the uptake of cationic amino acids. We show that an NPT from Toxoplasma gondii (TgNPT1) is a selective arginine transporter that is essential for parasite survival and virulence. We also demonstrate that a homologue of TgNPT1 from the malaria parasite Plasmodium berghei (PbNPT1), shown previously to be essential for the sexual gametocyte stage of the parasite, is a cationic amino acid transporter. This reveals a role for cationic amino acid scavenging in gametocyte biology. Our study demonstrates a critical role for amino acid transporters in the survival, virulence and life cycle progression of these parasites.
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Esther
authors.initials: E
authors.lastname: Rajendran
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Sanduni V
authors.initials: SV
authors.lastname: Hapuarachchi
authors.affiliation: College of Public Health, Medical and Veterinary Sciences, James Cook University, Smithfield, Queensland 4878, Australia.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Miller
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fairweather
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Yeping
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Queensland Tropical Health Alliance Research Laboratory, Australian Institute of Tropical Health and Medicine, James Cook University, Smithfield, Queensland 4878, Australia.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Smith
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Cockburn
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bröer
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Kiaran
authors.initials: K
authors.lastname: Kirk
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Giel G
authors.identifier: 0000-0003-2455-9821
authors.initials: GG
authors.lastname: van Dooren
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000378:metabolism*; D000818:Animals; D016782:Apicomplexa / Q000254:growth & development / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005718:Gametogenesis / Q000502:physiology; D008018:Life Cycle Stages / Q000502:physiology; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009865:Oocytes / Q000378:metabolism; D010271:Parasites / Q000254:growth & development / Q000378:metabolism*; D010962:Plasmodium berghei / Q000254:growth & development / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000378:metabolism*; D014122:Toxoplasma / Q000254:growth & development / Q000378:metabolism
chemical_list: D026923:Amino Acid Transport Systems, Basic; D026901:Membrane Transport Proteins; D015800:Protozoan Proteins; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D001120:Arginine