Positional dynamics and glycosomal recruitment of developmental regulators during trypanosome differentiation

Szö Ő Rbalazs, Balázs and Simon, Dorina V. and Rojas, Federico and Young, Julie and Robinson, Derrick R. and Krüger, Timothy and Engstler, Markus and Matthews, Keith R. (2019) Positional dynamics and glycosomal recruitment of developmental regulators during trypanosome differentiation. MBio, 10 (4): e00875-19. ISSN 2161-2129

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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, Tb- PIP39, 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.

Item Type:
Journal Article
Journal or Publication Title:
MBio
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2400/2404
Subjects:
?? developmentdifferentiationglycosomeorganelleparasitetrypanosomemicrobiologyvirology ??
ID Code:
212988
Deposited By:
Deposited On:
16 Jan 2024 09:40
Refereed?:
Yes
Published?:
Published
Last Modified:
16 Jan 2024 09:40