Aquaglyceroporins Are the Entry Pathway of Boric Acid in Trypanosoma brucei

Marsiccobetre, Sabrina; Rodrı́guez-Acosta, Alexis; Läng, Florian; Figarella, Katherine; Uzcátegui, Néstor L.

doi:10.1016/j.bbamem.2017.01.011

Cited by 7 publications

(8 citation statements)

References 44 publications

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“…b . brucei AQPs reveals their ability to transport water, mass: 18 Da; ammonia, mass: 17 Da [18]; boric acid, mass: 62 Da [19]; glycerol, mass: 92 Da [20] and some forms of trivalent arsenic, mass: 83–198 Da; and trivalent antimony, mass: 122–292 Da [21]. AQP2 gene-knockout in T .…”

Section: Introductionmentioning

confidence: 99%

Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity

et al. 2017

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Aquaglyceroporins (AQPs) transport water and glycerol and play important roles in drug-uptake in pathogenic trypanosomatids. For example, AQP2 in the human-infectious African trypanosome, Trypanosoma brucei gambiense, is responsible for melarsoprol and pentamidine-uptake, and melarsoprol treatment-failure has been found to be due to AQP2-defects in these parasites. To further probe the roles of these transporters, we assembled a T. b. brucei strain lacking all three AQP-genes. Triple-null aqp1-2-3 T. b. brucei displayed only a very moderate growth defect in vitro, established infections in mice and recovered effectively from hypotonic-shock. The aqp1-2-3 trypanosomes did, however, display glycerol uptake and efflux defects. They failed to accumulate glycerol or to utilise glycerol as a carbon-source and displayed increased sensitivity to salicylhydroxamic acid (SHAM), octyl gallate or propyl gallate; these inhibitors of trypanosome alternative oxidase (TAO) can increase intracellular glycerol to toxic levels. Notably, disruption of AQP2 alone generated cells with glycerol transport defects. Consistent with these findings, AQP2-defective, melarsoprol-resistant clinical isolates were sensitive to the TAO inhibitors, SHAM, propyl gallate and ascofuranone, relative to melarsoprol-sensitive reference strains. We conclude that African trypanosome AQPs are dispensable for viability and osmoregulation but they make important contributions to drug-uptake, glycerol-transport and respiratory-inhibitor sensitivity. We also discuss how the AQP-dependent inverse sensitivity to melarsoprol and respiratory inhibitors described here might be exploited.

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Section: Introductionmentioning

confidence: 99%

Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity

et al. 2017

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“…injection of 10 ng of cRNA and measurements between days 2–4 p.i. The standard iso-osmotic oocyte swelling assay for solute permeability measurements in X. laevis oocytes is affected by the water transport capacity of the assayed aquaglyceroporin 16,26,30 . To evaluate if a similar phenomenon can also occur in R. marina oocytes, TbAQP2 and TbAQP3 were chosen to be tested for glycerol permeability, as examples of aquaglyceroporins with high and middle permeability for water (Figs 1 and 2).…”

Section: Resultsmentioning

confidence: 99%

“…Under these conditions, a glycerol gradient is created maintaining the iso-osmolarity. The influx of glycerol across the aquaglyceroporin into the oocytes changes the inside osmolarity of the cells and produces a concomitant water entry, leading to the oocyte’s swelling proportionally to its glycerol permeability 16,17,26,30,38 . As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Toad ovary removal and oocytes obtaining were performed as previously described with some modifications 16,24–28,41 . Briefly, ovarian tissue was surgically obtained from adult females of R. marina under anaesthesia (0.23% 3-aminobenzoic ethyl ester acid).…”

Section: Methodsmentioning

confidence: 99%

“…The standard oocytes swelling assay was performed as previously described 12,16,26,30,38,41 . The assay has two modalities: the standard oocytes hypo-osmotic swelling assay to determine water permeability (Pf) and the standard oocytes iso-osmotic swelling assay that serves to measure solute permeability (Ps).…”

Section: Methodsmentioning

confidence: 99%

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Rhinella marina oocytes: a suitable alternative expression system for functional characterization of aquaglyceroporins

Rojas

Ortiz

Rodríguez

et al. 2019

Sci Rep

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Amphibian oocytes have been extensively used for heterologous expression of membrane proteins for studying their biochemical and biophysical properties. So far, Xenopus laevis is the main amphibian used as oocytes source to express aquaglyceroporins in order to assess water and solutes permeability. However, this well-established amphibian model represents a threat to the biodiversity in many countries, especially in those from tropical regions. For that reason, the import of Xenopus laevis is subjected to strict control, which essentially has restricted its use in these regions. Therefore, a wider variety of expression systems for aquaglyceroporins is needed. Rhinella marina is extensively distributed in the Americas and its native range spreads from South America to Texas, US. Here we report the use of Rhinella marina oocytes as an alternative expression system for aquaglyceroporins and demonstrated its suitability to determine the permeability to water and non-ionic solutes. Rhinella marina oocytes were able to functionally express channels from human and the protozoan pathogen Trypanosoma brucei, two very distant organisms on the evolutionary scale. Permeability values obtained from Rhinella marina oocytes expressing members of aquaporin family were similar and comparable to those values reported in the literature for the same channels expressed in Xenopus laevis oocytes.

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Approaches for modifying cellular cholesterol levels and their application to mechanistic studies: Examples from the ion channel field

Rosenhouse‐Dantsker¹,

Slayden²,

Bukiya³

2022

Cholesterol

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Aquaglyceroporins Are the Entry Pathway of Boric Acid in Trypanosoma brucei

Cited by 7 publications

References 44 publications

Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity

Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity

Rhinella marina oocytes: a suitable alternative expression system for functional characterization of aquaglyceroporins

Approaches for modifying cellular cholesterol levels and their application to mechanistic studies: Examples from the ion channel field

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