The Glycosylphosphatidylinositol-PLC in Trypanosoma brucei Forms a Linear Array on the Exterior of the Flagellar Membrane Before and After Activation

Hanrahan, Orla; Webb, Helena; O’Byrne, Robert; Brabazon, Elaine D.; Treumann, Achim; Sunter, Jack D.; Carrington, Mark; Voorheis, H. Paul

doi:10.1371/journal.ppat.1000468

Cited by 24 publications

(32 citation statements)

References 64 publications

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“…As an example, conflicting evidence for surface exposure of GPI-PLC has been reported (74,75). We observe a Bound/Input ratio Ͻ1 for this protein (supplemental Table S1), supporting intracellular localization.…”

Section: Cell Surface Proteome Analyses Distinguish Between Cellsupporting

confidence: 72%

Cell Surface Proteomics Provides Insight into Stage-Specific Remodeling of the Host-Parasite Interface in Trypanosoma brucei*

Shimogawa

Saada

Vashisht

et al. 2015

Molecular & Cellular Proteomics

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African trypanosomes are devastating human and animal pathogens transmitted by tsetse flies between mammalian hosts. The trypanosome surface forms a critical host interface that is essential for sensing and adapting to diverse host environments. However, trypanosome surface protein composition and diversity remain largely unknown. Here, we use surface labeling, affinity purification, and proteomic analyses to describe cell surface proteomes from insect-stage and mammalian bloodstreamstage Trypanosoma brucei. The cell surface proteomes contain most previously characterized surface proteins. We additionally identify a substantial number of novel proteins, whose functions are unknown, indicating the parasite surface proteome is larger and more diverse than generally appreciated. We also show stage-specific expression for individual paralogs within several protein families, suggesting that fine-tuned remodeling of the parasite surface allows adaptation to diverse host environments, while still fulfilling universally essential cellular needs. Our surface proteome analyses complement existing transcriptomic, proteomic, and in silico analyses by highlighting proteins that are surface-exposed and thereby provide a major step forward in defining the hostparasite interface. Molecular & Cellular

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Section: Cell Surface Proteome Analyses Distinguish Between Cellsupporting

confidence: 72%

Cell Surface Proteomics Provides Insight into Stage-Specific Remodeling of the Host-Parasite Interface in Trypanosoma brucei*

Shimogawa

Saada

Vashisht

et al. 2015

Molecular & Cellular Proteomics

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“…A rather similar distribution along the flagellum has been described for the GPI-anchored phospholipase C of T. brucei [55]. Although mainly lipid-driven, several factors have been proposed to assist in the formation and stabilization of membrane domains, including protein-lipid and protein-protein interactions.…”

Section: Lipid Domains As Pillars Of Membrane Organizationmentioning

confidence: 57%

The Trypanosoma cruzi Surface, a Nanoscale Patchwork Quilt

Mucci

Lantos

Buscaglia

et al. 2017

Trends in Parasitology

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The Trypanosoma cruzi trypomastigote membrane provides a major protective role against mammalian host-derived defense mechanisms while allowing the parasite to interact with different cell types and trigger pathogenesis. This surface has been historically appreciated as a rather unstructured ‘coat’, mainly consisting of a continuous layer of glycolipids and heavily O-glycosylated mucins, occasionally intercalated with different developmentally-regulated molecules displaying adhesive and/or enzymatic properties. Recent findings, however, indicate that the trypomastigote membrane is made up of multiple, densely packed and discrete 10–150 nm lipid-driven domains bearing different protein composition; hence resembling a highly organized ‘patchwork quilt’ design. Here, we discuss different aspects underlying the biogenesis, assembly and dynamics of this cutting edge fashion outfit, as well as its functional implications.

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“…1D); the 50% effective growth-inhibitory concentration (EC 50 ) was increased almost 2-fold relative to wild-type cells for melarsoprol and by more than 15-fold for pentamidine. Thus, aqp2 null cells are indistinguishable from aqp2/aqp3 null cells (5) in terms of EC 50 for either of these drugs.…”

mentioning

confidence: 90%

Aquaglyceroporin 2 controls susceptibility to melarsoprol and pentamidine in African trypanosomes

Baker

Glover

Munday

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

143

276

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African trypanosomes cause sleeping sickness in humans, a disease that is typically fatal without chemotherapy. Unfortunately, drug resistance is common and melarsoprol-resistant trypanosomes often display cross-resistance to pentamidine. Although melarsoprol/pentamidine cross-resistance (MPXR) has been an area of intense interest for several decades, our understanding of the underlying mechanisms remains incomplete. Recently, a locus encoding two closely related aquaglyceroporins, AQP2 and AQP3, was linked to MPXR in a high-throughput loss-of-function screen. Here, we show that AQP2 has an unconventional "selectivity filter." AQP2-specific gene knockout generated MPXR trypanosomes but did not affect resistance to a lipophilic arsenical, whereas recombinant AQP2 reversed MPXR in cells lacking native AQP2 and AQP3. AQP2 was also shown to be disrupted in a laboratory-selected MPXR strain. Both AQP2 and AQP3 gained access to the surface plasma membrane in insect life-cycle-stage trypanosomes but, remarkably, AQP2 was specifically restricted to the flagellar pocket in the bloodstream stage. We conclude that the unconventional aquaglyceroporin, AQP2, renders cells sensitive to both melarsoprol and pentamidine and that loss of AQP2 function could explain cases of innate and acquired MPXR.

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The Glycosylphosphatidylinositol-PLC in Trypanosoma brucei Forms a Linear Array on the Exterior of the Flagellar Membrane Before and After Activation

Cited by 24 publications

References 64 publications

Cell Surface Proteomics Provides Insight into Stage-Specific Remodeling of the Host-Parasite Interface in Trypanosoma brucei*

Cell Surface Proteomics Provides Insight into Stage-Specific Remodeling of the Host-Parasite Interface in Trypanosoma brucei*

The Trypanosoma cruzi Surface, a Nanoscale Patchwork Quilt

Aquaglyceroporin 2 controls susceptibility to melarsoprol and pentamidine in African trypanosomes

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