Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation

ABSTRACT Glycosomes are peroxisome-related organelles that compartmentalize the glycolytic enzymes in kinetoplastid parasites. These organelles are developmentally regulated in their number and composition, allowing metabolic adaptation to the parasite’s needs in the blood of mammalian hosts or with...

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Autores principales:	Balázs Szöőr, Dorina V. Simon, Federico Rojas, Julie Young, Derrick R. Robinson, Timothy Krüger, Markus Engstler, Keith R. Matthews
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	development differentiation organelle parasite trypanosome glycosome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/db74b9b8f9794d29b042d9f4235b3304
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spelling	oai:doaj.org-article:db74b9b8f9794d29b042d9f4235b33042021-11-15T16:22:09ZPositional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation10.1128/mBio.00875-192150-7511https://doaj.org/article/db74b9b8f9794d29b042d9f4235b33042019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00875-19https://doaj.org/toc/2150-7511ABSTRACT Glycosomes are peroxisome-related organelles that compartmentalize the glycolytic enzymes in kinetoplastid parasites. These organelles are developmentally regulated in their number and composition, allowing metabolic adaptation to the parasite’s needs in the blood of mammalian hosts or within their arthropod vector. A protein phosphatase cascade regulates differentiation between parasite developmental forms, comprising a tyrosine phosphatase, Trypanosoma brucei PTP1 (TbPTP1), which dephosphorylates and inhibits a serine threonine phosphatase, TbPIP39, which promotes differentiation. When TbPTP1 is inactivated, TbPIP39 is activated and during differentiation becomes located in glycosomes. Here we have tracked TbPIP39 recruitment to glycosomes during differentiation from bloodstream “stumpy” forms to procyclic forms. Detailed microscopy and live-cell imaging during the synchronous transition between life cycle stages revealed that in stumpy forms, TbPIP39 is located at a periflagellar pocket site closely associated with TbVAP, which defines the flagellar pocket endoplasmic reticulum. TbPTP1 is also located at the same site in stumpy forms, as is REG9.1, a regulator of stumpy-enriched mRNAs. This site provides a molecular node for the interaction between TbPTP1 and TbPIP39. Within 30 min of the initiation of differentiation, TbPIP39 relocates to glycosomes, whereas TbPTP1 disperses to the cytosol. Overall, the study identifies a “stumpy regulatory nexus” (STuRN) that coordinates the molecular components of life cycle signaling and glycosomal development during transmission of Trypanosoma brucei. IMPORTANCE African trypanosomes are parasites of sub-Saharan Africa responsible for both human and animal disease. The parasites are transmitted by tsetse flies, and completion of their life cycle involves progression through several development steps. The initiation of differentiation between blood and tsetse fly forms is signaled by a phosphatase cascade, ultimately trafficked into peroxisome-related organelles called glycosomes that are unique to this group of organisms. Glycosomes undergo substantial remodeling of their composition and function during the differentiation step, but how this is regulated is not understood. Here we identify a cytological site where the signaling molecules controlling differentiation converge before the dispersal of one of them into glycosomes. In combination, the study provides the first insight into the spatial coordination of signaling pathway components in trypanosomes as they undergo cell-type differentiation.Balázs SzöőrDorina V. SimonFederico RojasJulie YoungDerrick R. RobinsonTimothy KrügerMarkus EngstlerKeith R. MatthewsAmerican Society for MicrobiologyarticledevelopmentdifferentiationorganelleparasitetrypanosomeglycosomeMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	development differentiation organelle parasite trypanosome glycosome Microbiology QR1-502
spellingShingle	development differentiation organelle parasite trypanosome glycosome Microbiology QR1-502 Balázs Szöőr Dorina V. Simon Federico Rojas Julie Young Derrick R. Robinson Timothy Krüger Markus Engstler Keith R. Matthews Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation
description	ABSTRACT Glycosomes are peroxisome-related organelles that compartmentalize the glycolytic enzymes in kinetoplastid parasites. These organelles are developmentally regulated in their number and composition, allowing metabolic adaptation to the parasite’s needs in the blood of mammalian hosts or within their arthropod vector. A protein phosphatase cascade regulates differentiation between parasite developmental forms, comprising a tyrosine phosphatase, Trypanosoma brucei PTP1 (TbPTP1), which dephosphorylates and inhibits a serine threonine phosphatase, TbPIP39, which promotes differentiation. When TbPTP1 is inactivated, TbPIP39 is activated and during differentiation becomes located in glycosomes. Here we have tracked TbPIP39 recruitment to glycosomes during differentiation from bloodstream “stumpy” forms to procyclic forms. Detailed microscopy and live-cell imaging during the synchronous transition between life cycle stages revealed that in stumpy forms, TbPIP39 is located at a periflagellar pocket site closely associated with TbVAP, which defines the flagellar pocket endoplasmic reticulum. TbPTP1 is also located at the same site in stumpy forms, as is REG9.1, a regulator of stumpy-enriched mRNAs. This site provides a molecular node for the interaction between TbPTP1 and TbPIP39. Within 30 min of the initiation of differentiation, TbPIP39 relocates to glycosomes, whereas TbPTP1 disperses to the cytosol. Overall, the study identifies a “stumpy regulatory nexus” (STuRN) that coordinates the molecular components of life cycle signaling and glycosomal development during transmission of Trypanosoma brucei. IMPORTANCE African trypanosomes are parasites of sub-Saharan Africa responsible for both human and animal disease. The parasites are transmitted by tsetse flies, and completion of their life cycle involves progression through several development steps. The initiation of differentiation between blood and tsetse fly forms is signaled by a phosphatase cascade, ultimately trafficked into peroxisome-related organelles called glycosomes that are unique to this group of organisms. Glycosomes undergo substantial remodeling of their composition and function during the differentiation step, but how this is regulated is not understood. Here we identify a cytological site where the signaling molecules controlling differentiation converge before the dispersal of one of them into glycosomes. In combination, the study provides the first insight into the spatial coordination of signaling pathway components in trypanosomes as they undergo cell-type differentiation.
format	article
author	Balázs Szöőr Dorina V. Simon Federico Rojas Julie Young Derrick R. Robinson Timothy Krüger Markus Engstler Keith R. Matthews
author_facet	Balázs Szöőr Dorina V. Simon Federico Rojas Julie Young Derrick R. Robinson Timothy Krüger Markus Engstler Keith R. Matthews
author_sort	Balázs Szöőr
title	Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation
title_short	Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation
title_full	Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation
title_fullStr	Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation
title_full_unstemmed	Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation
title_sort	positional dynamics and glycosomal recruitment of developmental regulators during trypanosome differentiation
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/db74b9b8f9794d29b042d9f4235b3304
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Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation

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