AQPX-cluster aquaporins and aquaglyceroporins are asymmetrically distributed in trypanosomes

Abstract

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.

TriTrypDB: An integrated functional genomics resource for kinetoplastida

“…Some of the TriTrypDB tools that are popularly used by researchers include the genome browser [ 83 , 90 ], GO enrichment [ 19 , 86 ] and BLAST [ 71 , 79 ]. In addition, researchers have utilized integrated datasets including MS-based proteomics [ 91 , 92 ], RNAi [ 87 ] and SNPs [ 93 ], implemented searches ranging from gene IDs [ 94 ], text/ keywords [ 76 , 94 ], EC numbers [ 95 ], protein features and properties such as InterPro domains, signal peptides and transmembrane domains [ 86 , 96 , 97 ], and the search strategy system [ 86 ] to ask their research questions or test their hypotheses.…”

“…Below are a few recent examples of how TriTrypDB data and tools have been utilized by the research community to conduct their own research. TriTrypDB genomes and annotations have been used to characterize individual genes [69][70][71][72][73] or gene families [74,75], identify orthologs across species [55,70,76], conduct genome-wide analyses to study genetic variations such as SNPs, CNVs and hybridization events [77][78][79], perform comparative genomic [80][81][82] and phylogenetic/ phylogenomic [82,83] analyses, and as reference genomes for the assembly and/or annotation of newly generated genomes [16,84]. Similarly, the genome assemblies and annotations have also been utilized for the analysis of differential gene expression [19,72,85], protein expression [85][86][87], the identification of post-translational modifications [72] and potential new genes missing in the official gene sets [88].…”

“…Some of the TriTrypDB tools that are popularly used by researchers include the genome browser [83,90], GO enrichment [19,86] and BLAST [71,79]. In addition, researchers have utilized integrated datasets including MS-based proteomics [91,92], RNAi [87] and SNPs [93], implemented searches ranging from gene IDs [94], text/ keywords [76,94], EC numbers [95],…”

Exploring aquaporin functions during changes in leaf water potential

“…The plant Kingdom has the greatest aquaporin diversity compared to the animal, fungi, eubacterial, archeabacterial or protista Kingdoms. For example, there are 121 aquaporin isoforms in some Brassica species ( Yuan et al., 2017 ), whereas humans and many other mammals have 13 different aquaporins, and many single-celled organisms have one or two different aquaporins ( Tanghe et al., 2006 ; Verkman, 2008 ; Tesan et al., 2021 ). Arabidopsis has 35 aquaporins, and different aquaporins are up or down regulated in response to varying environmental conditions in different cells and tissues ( Jang et al., 2004 ).…”

Down the membrane hole: Ion channels in protozoan parasites

“…AQPs are considered major intrinsic proteins (MIPs), membrane channels that mediate the exchange of water and small solutes. As such, they also play a role in permeability to antiparasitic compounds and have been postulated as potential drug targets [ 130 , 139 ]. In Leishmania [ 132 ] and T .…”