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FRONTIERS IN BIOSCIENCE 4 ? SEPTEMBER 13 to 15, 2023 - Decoding AQPX Channels: Understanding selective transport and localization of Trypanosoma cruzi aquaporins
Congreso
Authorship:
Ramoa, Ursula ; VITALI, VICTORIA ANDREA ; Zerbetto de Palma, Gerardo ; Canessa Fortuna, Agustina ; Tesan, Fiorella C ; Bredeston, Luis ; Chiribao, María Laura ; Alleva, KarinaDate:
2023Publishing House and Editing Place:
FRONTIERS IN BIOSCIENCE 4 ? SEPTEMBER 13 to 15, 2023Summary *
MIP channels (major intrinsic protein), also known as aquaporins, are multifunctional channels primarily responsible for water transport. However, certain MIP channels have been shown to transport various solutes, including glycerol, urea, ammonium, and ions. Recently, there has been growing interest in exploiting aquaporins as cellular entry pathways for molecules with pharmacological functions, highlighting the potential of MIP channels in parasites as therapeutic targets. Our work focuses on the diversification of aquaporins (AQPs) in parasites, with a particular emphasis on understanding the structure-function relationships governing the selectivity transport of AQPs in Trypanosoma cruzi. Recently, we described that TcAQPs belong to a functionally uncharacterized group, which we named AQPX (Tesan et al. Commun Biol, 2021). Unlike known AQPs, the AQPX channels possess a distinct selectivity filter, and their permeation profile remains unknown. Among the four AQPX channels in Trypanosoma cruzi, only TcAQPα has been partially studied (Montalvetti et al, JBC 2004), while the other three channels lack functional investigations. It was also confirmed the presence of mRNA for all four TcAQPs in the three stages of T. cruzi (Diaz-Viraqué et al., bioRxiv 2023). Our preliminary experimental evidence suggests that all four AQPX channels in T. cruzi may have an intracellular localization, consistent with TcAQPα. Currently, we are studying the localization and transport of TcAQPα, TcAQPβ, TcAQPγ and TcAQPδ in heterologous expression systems (S. cerevisiae and X. laevis oocytes). Additionally, we conduct atomistic molecular dynamics experiments which suggest that these four channels are capable of transporting water. Further investigations are underway to elucidate the functional implications of these AQPX channels and their potential as therapeutic targets against trypanosomiasis. Information provided by the agent in SIGEVAKey Words
STRUCTURE-FUNCTION RELATIONSHIPSMULTIFUNCTIONAL CHANNELAQUAPORINSTRYPANOSOMA CRUZI