An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei

Fucose is a common component of eukaryotic cell-surface glycoconjugates, generally added by Golgi-resident fucosyltransferases. Whereas fucosylated glycoconjugates are rare in kinetoplastids, the biosynthesis of the nucleotide sugar GDP-Fuc has been shown to be essential in Trypanosoma brucei. Here...

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Autores principales:	Giulia Bandini, Sebastian Damerow, Maria Lucia Sempaio Guther, Hongjie Guo, Angela Mehlert, Jose Carlos Paredes Franco, Stephen Beverley, Michael AJ Ferguson
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	kinetoplastid glycobiology mitochondria fucosyltranferase Trypanosoma Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1f659dfe9a5e4c328ce7727d0febf88d
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spelling	oai:doaj.org-article:1f659dfe9a5e4c328ce7727d0febf88d2021-12-01T10:57:48ZAn essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei10.7554/eLife.702722050-084Xe70272https://doaj.org/article/1f659dfe9a5e4c328ce7727d0febf88d2021-08-01T00:00:00Zhttps://elifesciences.org/articles/70272https://doaj.org/toc/2050-084XFucose is a common component of eukaryotic cell-surface glycoconjugates, generally added by Golgi-resident fucosyltransferases. Whereas fucosylated glycoconjugates are rare in kinetoplastids, the biosynthesis of the nucleotide sugar GDP-Fuc has been shown to be essential in Trypanosoma brucei. Here we show that the single identifiable T. brucei fucosyltransferase (TbFUT1) is a GDP-Fuc: β-D-galactose α-1,2-fucosyltransferase with an apparent preference for a Galβ1,3GlcNAcβ1-O-R acceptor motif. Conditional null mutants of TbFUT1 demonstrated that it is essential for both the mammalian-infective bloodstream form and the insect vector-dwelling procyclic form. Unexpectedly, TbFUT1 was localized in the mitochondrion of T. brucei and found to be required for mitochondrial function in bloodstream form trypanosomes. Finally, the TbFUT1 gene was able to complement a Leishmania major mutant lacking the homologous fucosyltransferase gene (Guo et al., 2021). Together these results suggest that kinetoplastids possess an unusual, conserved and essential mitochondrial fucosyltransferase activity that may have therapeutic potential across trypanosomatids.Giulia BandiniSebastian DamerowMaria Lucia Sempaio GutherHongjie GuoAngela MehlertJose Carlos Paredes FrancoStephen BeverleyMichael AJ FergusoneLife Sciences Publications LtdarticlekinetoplastidglycobiologymitochondriafucosyltranferaseTrypanosomaMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	kinetoplastid glycobiology mitochondria fucosyltranferase Trypanosoma Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	kinetoplastid glycobiology mitochondria fucosyltranferase Trypanosoma Medicine R Science Q Biology (General) QH301-705.5 Giulia Bandini Sebastian Damerow Maria Lucia Sempaio Guther Hongjie Guo Angela Mehlert Jose Carlos Paredes Franco Stephen Beverley Michael AJ Ferguson An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei
description	Fucose is a common component of eukaryotic cell-surface glycoconjugates, generally added by Golgi-resident fucosyltransferases. Whereas fucosylated glycoconjugates are rare in kinetoplastids, the biosynthesis of the nucleotide sugar GDP-Fuc has been shown to be essential in Trypanosoma brucei. Here we show that the single identifiable T. brucei fucosyltransferase (TbFUT1) is a GDP-Fuc: β-D-galactose α-1,2-fucosyltransferase with an apparent preference for a Galβ1,3GlcNAcβ1-O-R acceptor motif. Conditional null mutants of TbFUT1 demonstrated that it is essential for both the mammalian-infective bloodstream form and the insect vector-dwelling procyclic form. Unexpectedly, TbFUT1 was localized in the mitochondrion of T. brucei and found to be required for mitochondrial function in bloodstream form trypanosomes. Finally, the TbFUT1 gene was able to complement a Leishmania major mutant lacking the homologous fucosyltransferase gene (Guo et al., 2021). Together these results suggest that kinetoplastids possess an unusual, conserved and essential mitochondrial fucosyltransferase activity that may have therapeutic potential across trypanosomatids.
format	article
author	Giulia Bandini Sebastian Damerow Maria Lucia Sempaio Guther Hongjie Guo Angela Mehlert Jose Carlos Paredes Franco Stephen Beverley Michael AJ Ferguson
author_facet	Giulia Bandini Sebastian Damerow Maria Lucia Sempaio Guther Hongjie Guo Angela Mehlert Jose Carlos Paredes Franco Stephen Beverley Michael AJ Ferguson
author_sort	Giulia Bandini
title	An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei
title_short	An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei
title_full	An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei
title_fullStr	An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei
title_full_unstemmed	An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei
title_sort	essential, kinetoplastid-specific gdp-fuc: β-d-gal α-1,2-fucosyltransferase is located in the mitochondrion of trypanosoma brucei
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/1f659dfe9a5e4c328ce7727d0febf88d
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An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei

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