{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:02:44Z","timestamp":1791453764713,"version":"4.3.3"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009816","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000}}],"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["DP150102883"],"award-info":[{"award-number":["DP150102883"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["DP200100483"],"award-info":[{"award-number":["DP200100483"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["GNT1128911"],"award-info":[{"award-number":["GNT1128911"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Intracellular parasites, such as the apicomplexan\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    , are adept at scavenging nutrients from their host. However, there is little understanding of how parasites sense and respond to the changing nutrient environments they encounter during an infection.\n                    <jats:italic>Tg<\/jats:italic>\n                    ApiAT1, a member of the apicomplexan ApiAT family of amino acid transporters, is the major uptake route for the essential amino acid L-arginine (Arg) in\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    . Here, we show that the abundance of\n                    <jats:italic>Tg<\/jats:italic>\n                    ApiAT1, and hence the rate of uptake of Arg, is regulated by the availability of Arg in the parasite\u2019s external environment, increasing in response to decreased [Arg]. Using a luciferase-based \u2018biosensor\u2019 strain of\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    , we demonstrate that the expression of\n                    <jats:italic>Tg<\/jats:italic>\n                    ApiAT1 varies between different organs within the host, indicating that parasites are able to modulate\n                    <jats:italic>Tg<\/jats:italic>\n                    ApiAT1-dependent uptake of Arg as they encounter different nutrient environments\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Finally, we show that Arg-dependent regulation of\n                    <jats:italic>Tg<\/jats:italic>\n                    ApiAT1 expression is post-transcriptional, mediated by an upstream open reading frame (uORF) in the\n                    <jats:italic>Tg<\/jats:italic>\n                    ApiAT1 transcript, and we provide evidence that the peptide encoded by this uORF is critical for mediating regulation. Together, our data reveal the mechanism by which an apicomplexan parasite responds to changes in the availability of a key nutrient.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009816","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T14:08:48Z","timestamp":1628172528000},"page":"e1009816","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Substrate-mediated regulation of the arginine transporter of Toxoplasma gondii"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8036-9531","authenticated-orcid":true,"given":"Esther","family":"Rajendran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2981-1934","authenticated-orcid":true,"given":"Cibelly","family":"Goulart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0927-4836","authenticated-orcid":true,"given":"Birte","family":"Steinh\u00f6fel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1711-0815","authenticated-orcid":true,"given":"Erick T.","family":"Tjhin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Gross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7467-1451","authenticated-orcid":true,"given":"Nicholas C.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5613-2622","authenticated-orcid":true,"given":"Kiaran","family":"Kirk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2455-9821","authenticated-orcid":true,"given":"Giel G.","family":"van Dooren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"issue":"2","key":"ppat.1009816.ref001","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ijpara.2013.09.003","article-title":"Exploitation of auxotrophies and metabolic defects in Toxoplasma as therapeutic approaches","volume":"44","author":"I. 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