Evolution, function and roles in drug sensitivity of trypanosome aquaglyceroporins

Quintana, Juan F.; Field, Mark C.

doi:10.1017/s0031182021000354

Cited by 6 publications

(3 citation statements)

References 68 publications

(104 reference statements)

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“…Perhaps because of its complex life cycle that imposed multiple bottlenecks and hence accelerated fixation of genotypes, T. brucei particularly stands out in some of these aspects. Recent interactions between T. brucei and humans can be linked to historical events and thus relatively accurately timed [26]. Weir and colleagues [27] estimated that human-infective T. brucei emerged within the past 10 000 years, coincident with establishment of a settled agricultural population, likely favoring human-human and human-domestic animal transmission.…”

Section: The Emergence Of African Sleeping Sicknessmentioning

confidence: 99%

African trypanosome strategies for conquering new hosts and territories: the end of monophyly?

Lukeš

Kachale

Votýpka

et al. 2022

Trends in Parasitology

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Section: The Emergence Of African Sleeping Sicknessmentioning

confidence: 99%

African trypanosome strategies for conquering new hosts and territories: the end of monophyly?

Lukeš

Kachale

Votýpka

et al. 2022

Trends in Parasitology

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“…In 2012 genome wide RNAi screens were used to identify pathways that facilitate anti-trypanosomal drug action and mechanisms involved in drug sensitivity and resistance. The article by Quintana and Field reviews the diversity, history and stability of TbAQP2 in terms of structure and function (Quintana and Field, 2021) and addresses the general question of the T. brucei protein stable as TbAQP2 possesses modified central core domains. TbAQP2 is the product of a trypanosome-specific duplication which has replaced the molecular NPA/NPA filter with NPS/NSA motif and the canonical aromatic/arginine (ar/R), while TbAQP2 is ubiquitylated and degraded via the lysosome.…”

Section: New Species and Drug Actionmentioning

confidence: 99%

Kinetoplastid cell biology and genetics, from the 2020 British Society for Parasitology Trypanosomiasis and Leishmaniasis symposium, Granada, Spain

et al. 2021

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The British Society for Parasitology (BSP) holds a biannual symposium devoted to the Kinetoplastids, and seeks to cover the full gamut of research into these important organisms, and alternates with the Woods Hole KMCB meeting that serves a similar community. While normally embedded within the main BSP Spring meeting, on several occasions the symposium has enjoyed the opportunity of being hosted on mainland Europe. In 2020 the BSP was fortunate to spend some time in Granada in Spain, where a superb meeting with excellent science in a spectacular setting was overshadowed by news of an emerging novel coronavirus. In this editorial we hope to have captured some of that excellent science and to highlight aspects of the many great papers and reviews in this special issue, as well as provide a few images from the meeting, which we hope for this who attended will bring back some fond memories.

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“…T. brucei MIPs were previously set as GLPs and T. cruzi MIPs as AQPs, whereas L. major MIPs were described in both groups 28 , 32 . Additionally, L. major and T. cruzi AQPs were regarded as TIP-related AQPs 31 , 33 . However, none of those studies focused specifically on the phylogeny of the Kinetoplastea class MIPs.…”

Section: Introductionmentioning

confidence: 99%

AQPX-cluster aquaporins and aquaglyceroporins are asymmetrically distributed in trypanosomes

et al. 2021

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Major Intrinsic Proteins (MIPs) are membrane channels that permeate water and other small solutes. Some trypanosomatid MIPs mediate the uptake of antiparasitic compounds, placing them as potential drug targets. However, a thorough study of the diversity of these channels is still missing. Here we place trypanosomatid channels in the sequence-function space of the large MIP superfamily through a sequence similarity network. This analysis exposes that trypanosomatid aquaporins integrate a distant cluster from the currently defined MIP families, here named aquaporin X (AQPX). Our phylogenetic analyses reveal that trypanosomatid MIPs distribute exclusively between aquaglyceroporin (GLP) and AQPX, being the AQPX family expanded in the Metakinetoplastina common ancestor before the origin of the parasitic order Trypanosomatida. Synteny analysis shows how African trypanosomes specifically lost AQPXs, whereas American trypanosomes specifically lost GLPs. AQPXs diverge from already described MIPs on crucial residues. Together, our results expose the diversity of trypanosomatid MIPs and will aid further functional, structural, and physiological research needed to face the potentiality of the AQPXs as gateways for trypanocidal drugs.

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Evolution, function and roles in drug sensitivity of trypanosome aquaglyceroporins

Abstract: Abstract

Cited by 6 publications

References 68 publications

African trypanosome strategies for conquering new hosts and territories: the end of monophyly?

African trypanosome strategies for conquering new hosts and territories: the end of monophyly?

Kinetoplastid cell biology and genetics, from the 2020 British Society for Parasitology Trypanosomiasis and Leishmaniasis symposium, Granada, Spain

AQPX-cluster aquaporins and aquaglyceroporins are asymmetrically distributed in trypanosomes

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