Most cited article - PubMed ID 32762841
Positively selected modifications in the pore of TbAQP2 allow pentamidine to enter Trypanosoma brucei
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.
- Keywords
- Aquaglyceroporin, Trypanosoma brucei, drug resistance, membrane trafficking, pentamidine, sleeping sickness,
- MeSH
- Aquaglyceroporins genetics MeSH
- Drug Resistance genetics MeSH
- Protozoan Proteins genetics MeSH
- Trypanocidal Agents pharmacology MeSH
- Trypanosoma drug effects metabolism MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Aquaglyceroporins MeSH
- Protozoan Proteins MeSH
- Trypanocidal Agents MeSH