Sterol targeting drugs reveal life cycle stage-specific differences in trypanosome lipid rafts

Abstract Cilia play important roles in cell signaling, facilitated by the unique lipid environment of a ciliary membrane containing high concentrations of sterol-rich lipid rafts. The African trypanosome Trypanosoma brucei is a single-celled eukaryote with a single cilium/flagellum. We tested whethe...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Aabha I. Sharma, Cheryl L. Olson, João I. Mamede, Felipe Gazos-Lopes, Conrad L. Epting, Igor C. Almeida, David M. Engman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c329ff680ea940cfbaf9daa2d9cbf096
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c329ff680ea940cfbaf9daa2d9cbf096
record_format	dspace
spelling	oai:doaj.org-article:c329ff680ea940cfbaf9daa2d9cbf0962021-12-02T16:06:24ZSterol targeting drugs reveal life cycle stage-specific differences in trypanosome lipid rafts10.1038/s41598-017-08770-92045-2322https://doaj.org/article/c329ff680ea940cfbaf9daa2d9cbf0962017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08770-9https://doaj.org/toc/2045-2322Abstract Cilia play important roles in cell signaling, facilitated by the unique lipid environment of a ciliary membrane containing high concentrations of sterol-rich lipid rafts. The African trypanosome Trypanosoma brucei is a single-celled eukaryote with a single cilium/flagellum. We tested whether flagellar sterol enrichment results from selective flagellar partitioning of specific sterol species or from general enrichment of all sterols. While all sterols are enriched in the flagellum, cholesterol is especially enriched. T. brucei cycles between its mammalian host (bloodstream cell), in which it scavenges cholesterol, and its tsetse fly host (procyclic cell), in which it both scavenges cholesterol and synthesizes ergosterol. We wondered whether the insect and mammalian life cycle stages possess chemically different lipid rafts due to different sterol utilization. Treatment of bloodstream parasites with cholesterol-specific methyl-β-cyclodextrin disrupts both membrane liquid order and localization of a raft-associated ciliary membrane calcium sensor. Treatment with ergosterol-specific amphotericin B does not. The opposite results were observed with ergosterol-rich procyclic cells. Further, these agents have opposite effects on flagellar sterol enrichment and cell metabolism in the two life cycle stages. These findings illuminate differences in the lipid rafts of an organism employing life cycle-specific sterols and have implications for treatment.Aabha I. SharmaCheryl L. OlsonJoão I. MamedeFelipe Gazos-LopesConrad L. EptingIgor C. AlmeidaDavid M. EngmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aabha I. Sharma Cheryl L. Olson João I. Mamede Felipe Gazos-Lopes Conrad L. Epting Igor C. Almeida David M. Engman Sterol targeting drugs reveal life cycle stage-specific differences in trypanosome lipid rafts
description	Abstract Cilia play important roles in cell signaling, facilitated by the unique lipid environment of a ciliary membrane containing high concentrations of sterol-rich lipid rafts. The African trypanosome Trypanosoma brucei is a single-celled eukaryote with a single cilium/flagellum. We tested whether flagellar sterol enrichment results from selective flagellar partitioning of specific sterol species or from general enrichment of all sterols. While all sterols are enriched in the flagellum, cholesterol is especially enriched. T. brucei cycles between its mammalian host (bloodstream cell), in which it scavenges cholesterol, and its tsetse fly host (procyclic cell), in which it both scavenges cholesterol and synthesizes ergosterol. We wondered whether the insect and mammalian life cycle stages possess chemically different lipid rafts due to different sterol utilization. Treatment of bloodstream parasites with cholesterol-specific methyl-β-cyclodextrin disrupts both membrane liquid order and localization of a raft-associated ciliary membrane calcium sensor. Treatment with ergosterol-specific amphotericin B does not. The opposite results were observed with ergosterol-rich procyclic cells. Further, these agents have opposite effects on flagellar sterol enrichment and cell metabolism in the two life cycle stages. These findings illuminate differences in the lipid rafts of an organism employing life cycle-specific sterols and have implications for treatment.
format	article
author	Aabha I. Sharma Cheryl L. Olson João I. Mamede Felipe Gazos-Lopes Conrad L. Epting Igor C. Almeida David M. Engman
author_facet	Aabha I. Sharma Cheryl L. Olson João I. Mamede Felipe Gazos-Lopes Conrad L. Epting Igor C. Almeida David M. Engman
author_sort	Aabha I. Sharma
title	Sterol targeting drugs reveal life cycle stage-specific differences in trypanosome lipid rafts
title_short	Sterol targeting drugs reveal life cycle stage-specific differences in trypanosome lipid rafts
title_full	Sterol targeting drugs reveal life cycle stage-specific differences in trypanosome lipid rafts
title_fullStr	Sterol targeting drugs reveal life cycle stage-specific differences in trypanosome lipid rafts
title_full_unstemmed	Sterol targeting drugs reveal life cycle stage-specific differences in trypanosome lipid rafts
title_sort	sterol targeting drugs reveal life cycle stage-specific differences in trypanosome lipid rafts
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c329ff680ea940cfbaf9daa2d9cbf096
work_keys_str_mv	AT aabhaisharma steroltargetingdrugsreveallifecyclestagespecificdifferencesintrypanosomelipidrafts AT cheryllolson steroltargetingdrugsreveallifecyclestagespecificdifferencesintrypanosomelipidrafts AT joaoimamede steroltargetingdrugsreveallifecyclestagespecificdifferencesintrypanosomelipidrafts AT felipegazoslopes steroltargetingdrugsreveallifecyclestagespecificdifferencesintrypanosomelipidrafts AT conradlepting steroltargetingdrugsreveallifecyclestagespecificdifferencesintrypanosomelipidrafts AT igorcalmeida steroltargetingdrugsreveallifecyclestagespecificdifferencesintrypanosomelipidrafts AT davidmengman steroltargetingdrugsreveallifecyclestagespecificdifferencesintrypanosomelipidrafts
_version_	1718385051869118464

Sterol targeting drugs reveal life cycle stage-specific differences in trypanosome lipid rafts

Ejemplares similares