Diversity in the MIP family and description of expanded groups in kinetoplastid parasites

ALLEVA KARINA

Mar del Plata

Congreso; Reunión Conjunta SAIC SAI&FAIC SAFIS 2022; 2022

Since the discovery of hAQP1, the paradigmatic exemplar of MIP family (Membrane Intrinsic Proteins) of channels, many homologous genes have been identified in archaea, bacteria, and different eukaryotic organisms. In most genomes there are multiple MIP genes with plants being the specimens where the greatest diversification has occurred. Understanding how such gene diversity emerged is still a challenge and an open question that entails the complexity of predicting the function of each sequence. In recent years, parasite aquaporins have been positioned as possible therapeutic targets based on the finding that MIP channels were able to internalize drugs of choice against Trypanosoma brucei and Leishmania spp. (i.e. pentamidine and antimonial compounds). This led us to carry out an exhaustive analysis of the diversity of the MIP family in trypanosomatids (Tesan et al., Commun Biol 4, 953 (2021)). Our phylogenetic analyzes revealed that trypanosomatid MIP channels are distributed exclusively in two groups: GLP or aquaglyceroporins, and a distant group that was not described until now, which we call AQPX. This group of aquaporins were already widespread in the Metakinetoplastina common ancestor before the origin of the parasitic order Trypanosomatida. Synteny studies show that African trypanosomes specifically lost the AQPX group, while American trypanosomes specifically lost GLP. GLP channels preferentially transport glycerol, while AQPX channels diverge from already described MIPs on crucial residues and present quite different selectivity filters that it is difficult to predict what transport function they may be fulfilling. The potential for AQPX channels to be, like GLPs, gateways for trypanocidal drugs makes studying them functionally and structurally highly relevant.