Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation

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...

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Main Authors: Balázs Szöőr, Dorina V. Simon, Federico Rojas, Julie Young, Derrick R. Robinson, Timothy Krüger, Markus Engstler, Keith R. Matthews
Format: Article
Language:English
Published: American Society for Microbiology 2019-07-01
Series:mBio
Subjects:
Online Access:https://doi.org/10.1128/mBio.00875-19
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spelling doaj-9aa3da00fc704734b08e04ad7cf9f4d32021-07-02T12:09:56ZengAmerican Society for MicrobiologymBio2150-75112019-07-01104e00875-1910.1128/mBio.00875-19Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome DifferentiationBalázs SzöőrDorina V. SimonFederico RojasJulie YoungDerrick R. RobinsonTimothy KrügerMarkus EngstlerKeith R. MatthewsAfrican 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.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.https://doi.org/10.1128/mBio.00875-19developmentdifferentiationorganelleparasitetrypanosomeglycosome
collection DOAJ
language English
format Article
sources DOAJ
author Balázs Szöőr
Dorina V. Simon
Federico Rojas
Julie Young
Derrick R. Robinson
Timothy Krüger
Markus Engstler
Keith R. Matthews
spellingShingle 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
mBio
development
differentiation
organelle
parasite
trypanosome
glycosome
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
series mBio
issn 2150-7511
publishDate 2019-07-01
description 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.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.
topic development
differentiation
organelle
parasite
trypanosome
glycosome
url https://doi.org/10.1128/mBio.00875-19
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