Evolution, function and roles in drug sensitivity of trypanosome aquaglyceroporins

Quintana, J. F. and Field, M. C. (2021) Evolution, function and roles in drug sensitivity of trypanosome aquaglyceroporins. Parasitology, 148(10), pp. 1137-1142. (doi: 10.1017/S0031182021000354) (PMID:33602349) (PMCID:PMC8311954)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Quintana, Dr Juan
• Authors: Quintana, J. F., and Field, M. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Parasitology
• Publisher: Cambridge University Press
• ISSN: 0031-1820
• ISSN (Online): 1469-8161
• Published Online: 19 February 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Parasitology 148(10): 1137-1142
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
310358		Molecular basis of pathogen-induced disruption of host circadian rhythms	Juan Quintana	Wellcome Trust (WELLCOTR)	221640/Z/20/Z	MVLS - Polyomics Facility