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2021-08-25Zeitschriftenartikel
Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii
dc.contributor.authorFairweather, Stephen J.
dc.contributor.authorRajendran, Esther
dc.contributor.authorBlume, Martin
dc.contributor.authorJaved, Kiran
dc.contributor.authorSteinhöfel, Birte
dc.contributor.authorMcConville, Malcolm J.
dc.contributor.authorKirk, Kiaran
dc.contributor.authorBröer, Stefan
dc.contributor.authorvan Dooren, Giel G.
dc.date.accessioned2024-06-10T15:13:18Z
dc.date.available2024-06-10T15:13:18Z
dc.date.issued2021-08-25none
dc.identifier.other10.1371/journal.ppat.1009835
dc.identifier.urihttp://edoc.rki.de/176904/11703
dc.description.abstractIntracellular parasites of the phylum Apicomplexa are dependent on the scavenging of essential amino acids from their hosts. We previously identified a large family of apicomplexan-specific plasma membrane-localized amino acid transporters, the ApiATs, and showed that the Toxoplasma gondii transporter TgApiAT1 functions in the selective uptake of arginine. TgApiAT1 is essential for parasite virulence, but dispensable for parasite growth in medium containing high concentrations of arginine, indicating the presence of at least one other arginine transporter. Here we identify TgApiAT6-1 as the second arginine transporter. Using a combination of parasite assays and heterologous characterisation of TgApiAT6-1 in Xenopus laevis oocytes, we demonstrate that TgApiAT6-1 is a general cationic amino acid transporter that mediates both the high-affinity uptake of lysine and the low-affinity uptake of arginine. TgApiAT6-1 is the primary lysine transporter in the disease-causing tachyzoite stage of T. gondii and is essential for parasite proliferation. We demonstrate that the uptake of cationic amino acids by TgApiAT6-1 is ‘trans-stimulated’ by cationic and neutral amino acids and is likely promoted by an inwardly negative membrane potential. These findings demonstrate that T. gondii has evolved overlapping transport mechanisms for the uptake of essential cationic amino acids, and we draw together our findings into a comprehensive model that highlights the finely-tuned, regulated processes that mediate cationic amino acid scavenging by these intracellular parasites.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleCoordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondiinone
dc.typearticle
dc.identifier.urnurn:nbn:de:0257-176904/11703-5
dc.type.versionpublishedVersionnone
local.edoc.container-titlePLOS Pathogensnone
local.edoc.container-issn1553-7374none
local.edoc.pages34none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://journals.plos.org/plospathogens/none
local.edoc.container-publisher-namePLOSnone
local.edoc.container-volume17none
local.edoc.container-issue8none
local.edoc.container-reportyear2021none
dc.description.versionPeer Reviewednone

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