Heme uptake by Leishmania amazonensis is mediated by the transmembrane protein LHR1.

Trypanosomatid protozoan parasites lack a functional heme biosynthetic pathway, so must acquire heme from the environment to survive. However, the molecular pathway responsible for heme acquisition by these organisms is unknown. Here we show that L. amazonensis LHR1, a homolog of the C. elegans plas...

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Autores principales:	Chau Huynh, Xiaojing Yuan, Danilo C Miguel, Rebecca L Renberg, Olga Protchenko, Caroline C Philpott, Iqbal Hamza, Norma W Andrews
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8a247c87896f4dc798eb7cceb901a990
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spelling	oai:doaj.org-article:8a247c87896f4dc798eb7cceb901a9902021-11-18T06:04:13ZHeme uptake by Leishmania amazonensis is mediated by the transmembrane protein LHR1.1553-73661553-737410.1371/journal.ppat.1002795https://doaj.org/article/8a247c87896f4dc798eb7cceb901a9902012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22807677/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Trypanosomatid protozoan parasites lack a functional heme biosynthetic pathway, so must acquire heme from the environment to survive. However, the molecular pathway responsible for heme acquisition by these organisms is unknown. Here we show that L. amazonensis LHR1, a homolog of the C. elegans plasma membrane heme transporter HRG-4, functions in heme transport. Tagged LHR1 localized to the plasma membrane and to endocytic compartments, in both L. amazonensis and mammalian cells. Heme deprivation in L. amazonensis increased LHR1 transcript levels, promoted uptake of the fluorescent heme analog ZnMP, and increased the total intracellular heme content of promastigotes. Conversely, deletion of one LHR1 allele reduced ZnMP uptake and the intracellular heme pool by approximately 50%, indicating that LHR1 is a major heme importer in L. amazonensis. Viable parasites with correct replacement of both LHR1 alleles could not be obtained despite extensive attempts, suggesting that this gene is essential for the survival of promastigotes. Notably, LHR1 expression allowed Saccharomyces cerevisiae to import heme from the environment, and rescued growth of a strain deficient in heme biosynthesis. Syntenic genes with high sequence identity to LHR1 are present in the genomes of several species of Leishmania and also Trypanosoma cruzi and Trypanosoma brucei, indicating that therapeutic agents targeting this transporter could be effective against a broad group of trypanosomatid parasites that cause serious human disease.Chau HuynhXiaojing YuanDanilo C MiguelRebecca L RenbergOlga ProtchenkoCaroline C PhilpottIqbal HamzaNorma W AndrewsPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 7, p e1002795 (2012)
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 Chau Huynh Xiaojing Yuan Danilo C Miguel Rebecca L Renberg Olga Protchenko Caroline C Philpott Iqbal Hamza Norma W Andrews Heme uptake by Leishmania amazonensis is mediated by the transmembrane protein LHR1.
description	Trypanosomatid protozoan parasites lack a functional heme biosynthetic pathway, so must acquire heme from the environment to survive. However, the molecular pathway responsible for heme acquisition by these organisms is unknown. Here we show that L. amazonensis LHR1, a homolog of the C. elegans plasma membrane heme transporter HRG-4, functions in heme transport. Tagged LHR1 localized to the plasma membrane and to endocytic compartments, in both L. amazonensis and mammalian cells. Heme deprivation in L. amazonensis increased LHR1 transcript levels, promoted uptake of the fluorescent heme analog ZnMP, and increased the total intracellular heme content of promastigotes. Conversely, deletion of one LHR1 allele reduced ZnMP uptake and the intracellular heme pool by approximately 50%, indicating that LHR1 is a major heme importer in L. amazonensis. Viable parasites with correct replacement of both LHR1 alleles could not be obtained despite extensive attempts, suggesting that this gene is essential for the survival of promastigotes. Notably, LHR1 expression allowed Saccharomyces cerevisiae to import heme from the environment, and rescued growth of a strain deficient in heme biosynthesis. Syntenic genes with high sequence identity to LHR1 are present in the genomes of several species of Leishmania and also Trypanosoma cruzi and Trypanosoma brucei, indicating that therapeutic agents targeting this transporter could be effective against a broad group of trypanosomatid parasites that cause serious human disease.
format	article
author	Chau Huynh Xiaojing Yuan Danilo C Miguel Rebecca L Renberg Olga Protchenko Caroline C Philpott Iqbal Hamza Norma W Andrews
author_facet	Chau Huynh Xiaojing Yuan Danilo C Miguel Rebecca L Renberg Olga Protchenko Caroline C Philpott Iqbal Hamza Norma W Andrews
author_sort	Chau Huynh
title	Heme uptake by Leishmania amazonensis is mediated by the transmembrane protein LHR1.
title_short	Heme uptake by Leishmania amazonensis is mediated by the transmembrane protein LHR1.
title_full	Heme uptake by Leishmania amazonensis is mediated by the transmembrane protein LHR1.
title_fullStr	Heme uptake by Leishmania amazonensis is mediated by the transmembrane protein LHR1.
title_full_unstemmed	Heme uptake by Leishmania amazonensis is mediated by the transmembrane protein LHR1.
title_sort	heme uptake by leishmania amazonensis is mediated by the transmembrane protein lhr1.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8a247c87896f4dc798eb7cceb901a990
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Heme uptake by Leishmania amazonensis is mediated by the transmembrane protein LHR1.

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