Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii.

Intracellular 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 transport...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Stephen J Fairweather, Esther Rajendran, Martin Blume, Kiran Javed, Birte Steinhöfel, Malcolm J McConville, Kiaran Kirk, Stefan Bröer, Giel G van Dooren
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/53e61d32b3994dd4b73f4ec8560f0c98
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:53e61d32b3994dd4b73f4ec8560f0c98
record_format	dspace
spelling	oai:doaj.org-article:53e61d32b3994dd4b73f4ec8560f0c982021-12-02T20:00:15ZCoordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii.1553-73661553-737410.1371/journal.ppat.1009835https://doaj.org/article/53e61d32b3994dd4b73f4ec8560f0c982021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009835https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Intracellular 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.Stephen J FairweatherEsther RajendranMartin BlumeKiran JavedBirte SteinhöfelMalcolm J McConvilleKiaran KirkStefan BröerGiel G van DoorenPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 8, p e1009835 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Stephen J Fairweather Esther Rajendran Martin Blume Kiran Javed Birte Steinhöfel Malcolm J McConville Kiaran Kirk Stefan Bröer Giel G van Dooren Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii.
description	Intracellular 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.
format	article
author	Stephen J Fairweather Esther Rajendran Martin Blume Kiran Javed Birte Steinhöfel Malcolm J McConville Kiaran Kirk Stefan Bröer Giel G van Dooren
author_facet	Stephen J Fairweather Esther Rajendran Martin Blume Kiran Javed Birte Steinhöfel Malcolm J McConville Kiaran Kirk Stefan Bröer Giel G van Dooren
author_sort	Stephen J Fairweather
title	Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii.
title_short	Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii.
title_full	Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii.
title_fullStr	Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii.
title_full_unstemmed	Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii.
title_sort	coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite toxoplasma gondii.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/53e61d32b3994dd4b73f4ec8560f0c98
work_keys_str_mv	AT stephenjfairweather coordinatedactionofmultipletransportersintheacquisitionofessentialcationicaminoacidsbytheintracellularparasitetoxoplasmagondii AT estherrajendran coordinatedactionofmultipletransportersintheacquisitionofessentialcationicaminoacidsbytheintracellularparasitetoxoplasmagondii AT martinblume coordinatedactionofmultipletransportersintheacquisitionofessentialcationicaminoacidsbytheintracellularparasitetoxoplasmagondii AT kiranjaved coordinatedactionofmultipletransportersintheacquisitionofessentialcationicaminoacidsbytheintracellularparasitetoxoplasmagondii AT birtesteinhofel coordinatedactionofmultipletransportersintheacquisitionofessentialcationicaminoacidsbytheintracellularparasitetoxoplasmagondii AT malcolmjmcconville coordinatedactionofmultipletransportersintheacquisitionofessentialcationicaminoacidsbytheintracellularparasitetoxoplasmagondii AT kiarankirk coordinatedactionofmultipletransportersintheacquisitionofessentialcationicaminoacidsbytheintracellularparasitetoxoplasmagondii AT stefanbroer coordinatedactionofmultipletransportersintheacquisitionofessentialcationicaminoacidsbytheintracellularparasitetoxoplasmagondii AT gielgvandooren coordinatedactionofmultipletransportersintheacquisitionofessentialcationicaminoacidsbytheintracellularparasitetoxoplasmagondii
_version_	1718375720867069952

Coordinated action of multiple transporters in the acquisition of essential cationic amino acids by the intracellular parasite Toxoplasma gondii.

Ejemplares similares