Evolution, function and roles in drug sensitivity of trypanosome aquaglyceroporins

Aquaglyceroporins (AQPs) are membrane proteins that function in osmoregulation and the uptake of low molecular weight solutes, in particular glycerol and urea. The AQP family is highly conserved, with two major subfamilies having arisen very early in prokaryote evolution and retained by eukaryotes....

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Bibliographic Details
Published in:Parasitology 2021-09, Vol.148 (10), p.1137-1142
Main Authors: Quintana, Juan F., Field, Mark C.
Format: Article
Language:English
Subjects:
Aquaglyceroporins - genetics
Aquaporin 2
Chemotherapy
Drug resistance
Drug Resistance - genetics
Eukaryotes
Evolution
Genomes
Glycerol
Laboratories
Low molecular weights
Membrane proteins
Molecular weight
Mutation
Osmoregulation
Parasites
Pentamidine
Proteins
Protozoan Proteins - genetics
Review
Sensitivity
Solutes
Trypanocidal Agents - pharmacology
Trypanosoma - drug effects
Trypanosoma - metabolism
Trypanosome
Urea
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Summary:Aquaglyceroporins (AQPs) are membrane proteins that function in osmoregulation and the uptake of low molecular weight solutes, in particular glycerol and urea. The AQP family is highly conserved, with two major subfamilies having arisen very early in prokaryote evolution and retained by eukaryotes. A complex evolutionary history indicates multiple lineage-specific expansions, losses and not uncommonly a complete loss. Consequently, the AQP family is highly evolvable and has been associated with significant events in life on Earth. In the African trypanosomes, a role for the AQP2 paralogue, in sensitivity to two chemotherapeutic agents, pentamidine and melarsoprol, is well established, albeit with the mechanisms for cell entry and resistance unclear until very recently. Here, we discuss AQP evolution, structure and mechanisms by which AQPs impact drug sensitivity, suggesting that AQP2 stability is highly sensitive to mutation while serving as the major uptake pathway for pentamidine.
ISSN:0031-1820
1469-8161
DOI:10.1017/S0031182021000354