Substrate-mediated regulation of the arginine transporter of Toxoplasma gondii

Rajendran, E; Clark, M; Goulart, C; Steinhöfel, B; Tjhin, ET; Smith, NC; Kirk, K; van Dooren, GG

Substrate-mediated regulation of the arginine transporter of Toxoplasma gondii

Rajendran, E Clark, M Goulart, C

Steinhöfel, B Tjhin, ET Smith, NC Kirk, K van Dooren, GG

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Publication Type:: Journal Article
Citation:: 2019, pp. 798967
Issue Date:: 2019-10-09

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Field	Value	Language
dc.contributor.author	Rajendran, E
dc.contributor.author	Clark, M
dc.contributor.author	Goulart, C https://orcid.org/0000-0003-2981-1934
dc.contributor.author	Steinhöfel, B
dc.contributor.author	Tjhin, ET
dc.contributor.author	Smith, NC
dc.contributor.author	Kirk, K
dc.contributor.author	van Dooren, GG
dc.date.accessioned	2022-02-11T04:16:27Z
dc.date.available	2022-02-11T04:16:27Z
dc.date.issued	2019-10-09
dc.identifier.citation	2019, pp. 798967
dc.identifier.uri	http://hdl.handle.net/10453/154403
dc.description.abstract	<jats:title>ABSTRACT</jats:title><jats:p>Intracellular parasites, such as the apicomplexan<jats:italic>Toxoplasma gondii</jats:italic>, 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.<jats:italic>Tg</jats:italic>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<jats:italic>T. gondii</jats:italic>. Here, we show that the abundance of<jats:italic>Tg</jats:italic>ApiAT1, and hence the rate of uptake of Arg, is regulated by the availability of Arg in the parasite’s external environment, increasing in response to decreased [Arg]. Using a luciferase-based ‘biosensor’ strain of<jats:italic>T. gondii</jats:italic>, we demonstrate that parasites vary the expression of<jats:italic>Tg</jats:italic>ApiAT1 in different organs within their host, indicating that parasites are able to modulate<jats:italic>Tg</jats:italic>ApiAT1-dependent uptake of Arg as they encounter different nutrient environments<jats:italic>in vivo</jats:italic>. Finally, we show that Arg-dependent regulation of<jats:italic>Tg</jats:italic>ApiAT1 expression is post-transcriptional, mediated by an upstream open reading frame (uORF) in the<jats:italic>Tg</jats:italic>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.</jats:p>
dc.language	en
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1128911
dc.relation.isbasedon	10.1101/798967
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.title	Substrate-mediated regulation of the arginine transporter of Toxoplasma gondii
dc.type	Journal Article
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	recently_added	*
dc.date.updated	2022-02-11T04:16:25Z

Abstract:

ABSTRACTIntracellular parasites, such as the apicomplexanToxoplasma gondii, 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.TgApiAT1, a member of the apicomplexan ApiAT family of amino acid transporters, is the major uptake route for the essential amino acid L-arginine (Arg) inT. gondii. Here, we show that the abundance ofTgApiAT1, and hence the rate of uptake of Arg, is regulated by the availability of Arg in the parasite’s external environment, increasing in response to decreased [Arg]. Using a luciferase-based ‘biosensor’ strain ofT. gondii, we demonstrate that parasites vary the expression ofTgApiAT1 in different organs within their host, indicating that parasites are able to modulateTgApiAT1-dependent uptake of Arg as they encounter different nutrient environmentsin vivo. Finally, we show that Arg-dependent regulation ofTgApiAT1 expression is post-transcriptional, mediated by an upstream open reading frame (uORF) in theTgApiAT1 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.

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http://hdl.handle.net/10453/154403